JP2004196822A - Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide triazaspiro[5.5]undecane derivatives, and a drug containing the same as the active ingredient. <P>SOLUTION: Triazaspiro[5.5]undecane derivatives of formula (I), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, or pharmaceutical compositions comprising them, as active ingredients (wherein R<SP>1</SP>is formula (II) or formula (III); R<SP>2</SP>is an alkyl or alkynyl etc.; R<SP>3</SP>, R<SP>4</SP>are each H, a (substituted) alkyl etc., or R<SP>3</SP>and R<SP>4</SP>together to form formula (IV); R<SP>5</SP>is H or an alkyl). Therefore the compounds of the formula (I) regulate the effect of chemokine/chemokine receptor, they are used for prevention and treatment of various inflammatory diseases, asthma, atopic dermatitis, urticaria, allergic diseases, nephritis, nephropathy, hepatitis, arthritis or rheumatoid arthritis etc. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

（式中、すべての記号は後記と同じ意味を表わす。）で示されるトリアザスピロ［５．５］ウンデカン誘導体、それらの四級アンモニウム塩、それらのＮ−オキシド、それらの非毒性塩、それらの製造方法、およびそれらを有効成分として含有する薬剤に関する。 The present invention relates to a triazaspiro [5.5] undecane derivative and a drug containing the same as an active ingredient.
More specifically, the general formula (I)

(Wherein all symbols have the same meanings as described below), triazaspiro [5.5] undecane derivatives, their quaternary ammonium salts, their N-oxides, their non-toxic salts, their production The present invention relates to a method and to medicaments containing them as active ingredients.

  Chemokines are known as basic proteins that have endogenous leukocyte chemotaxis and activation, and have strong heparin-binding properties. Chemokines are now thought to be involved not only in inflammation and specific leukocyte infiltration during immune responses, but also in development, homing of lymphocytes under physiological conditions, migration of blood cell progenitors and somatic cells. Have been.

  The differentiation, proliferation, and cell death of blood cells are controlled by various cytokines. In vivo, inflammation is observed locally, and lymphocyte differentiation, maturation, and the like are performed at specific sites. That is, a variety of required cells migrate to a specific site and accumulate, causing a series of inflammation and immune reactions. Therefore, in addition to cell differentiation, proliferation and death, cell migration is also an essential phenomenon for the immune system.

  The migration of blood cells in a living body begins with the transition of hematopoiesis that begins in the AGM region to the permanent hematopoiesis in the bone marrow via the fetal liver during development. Furthermore, precursor cells of T cells and thymic dendritic cells migrate from the fetal liver and bone marrow to the thymus, and differentiate into cells in a thymic environment. T cells that have undergone clonal selection migrate to secondary lymphoid tissues and participate in the immune response in the periphery. The Langerhans cells of the skin that have captured, activated and differentiated the antigen migrate to the T cell region of the local lymph node and activate naive T cells as dendritic cells. The memory T cells home again to lymph nodes via lymphatic vessels and blood vessels. In addition, B cells, intestinal T cells in the intestinal tract, γδ T cells, NKT cells, and dendritic cells migrate and differentiate from bone marrow without passing through the thymus, and are involved in the immune response.

Chemokines are deeply involved in such various cell migration. For example, MIP3β, SLC and its receptor CCR7 are required for mature dendritic cells that have captured antigen to migrate and home to local lymphoid tissues in order to efficiently meet naive and memory T cells. It plays an important role in In the secondary lymph nodes of PLT mice deficient in SLC expression, almost no T cells and dendritic cells required to control an antigen-specific immune response are observed (J. Exp. Med., 189 ( 3), 451 (1999);

MDC, TARC and its receptor CCR4 play an important role in the local migration of Th2 cells in immune and inflammatory reactions involving Th2 cells. In a rat fulminant hepatitis model (P. acnes + LPS), anti-TARC antibody suppressed an increase in blood ALT level and an increase in liver TNFα and FasL expression levels, and further improved rat mortality (J. Clin). Invest., 102 , 1933 (1998); In a mouse OVA-induced airway hyperreactivity model, anti-MDC antibody reduced the number of eosinophils accumulated in the lung interstitium and suppressed airway hypersensitivity (J. Immunology, 163 , 403 (1999); Non-Patent Document 3). ).

MCP-1 and its receptor, CCR2, are involved in macrophage infiltration into inflammatory sites. Anti-MCP-1 antibody showed an inhibitory effect on monocyte and macrophage infiltration into glomeruli in a rat anti-Thy1.1 antibody nephritis model (Kidney Int., 51 , 770 (1997); Non-Patent Document 4). .

  As described above, chemokine receptors are expressed in various specific cells at a specific time, and the effector cells accumulate at locations where chemokines are produced. Are involved.

  Acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV) infection, is one of the most coveted diseases in recent years. It is. Once HIV infection has been established in CD4 positive cells, which are major target cells, HIV repeats proliferation in the patient's body and eventually catastrophically destroys T cells that control immune functions. In this process, the immune function gradually decreases, and various immunodeficiency states such as fever, diarrhea, and swelling of lymph nodes are exhibited, and various opportunistic infections such as carinii pneumonia are easily caused. It is well known that such a condition is the onset of AIDS, which induces malignant tumors such as carbodisarcoma and becomes serious.

  At present, various methods for preventing and treating AIDS include, for example, (1) suppression of HIV proliferation by administration of a reverse transcriptase inhibitor or a protease inhibitor, and (2) opportunistic infection by administration of an immunostimulating drug. Prevention, mitigation, etc. are being attempted.

HIV mainly infects helper T cells, which are central to the immune system. At that time, it has been known from 1985 to use the membrane protein CD4 expressed on the membrane of T cells (Cell, 52 , 631 (1985); Non-Patent Document 5). The CD4 molecule is composed of 433 amino acid residues. In addition to mature helper T cells, macrophages, some B cells, vascular endothelial cells, Langerhans cells in skin tissue, dendritic cells in lymphoid tissue, glial cells in central nervous system And the like. However, as it became clear that HIV infection cannot be established by CD4 molecules alone, the possibility of the presence of factors other than CD4 molecules involved in HIV infection of cells has been suggested.

In 1996, a cell membrane protein called Fusin was identified as a factor related to HIV infection other than the CD4 molecule (Science, 272 , 872 (1996); Non-Patent Document 6). This Fusin molecule was proved to be a receptor for Stromal Derived Factor-1 (abbreviated as SDF-1) (that is, CXCR4). Furthermore, it has been demonstrated that SDF-1 specifically suppresses T cell-tropic (X4) HIV infection in vitro (Nature, 382 , 829 (1996); Non-Patent Document 7, Nature, 382 , 833). (1996); That is, it is considered that the binding of SDF-1 to CXCR4 prior to HIV deprived HIV of a foothold for infecting cells and inhibited HIV infection.

At the same time, it was discovered that another chemokine receptor, CCR5, a receptor for RANTES, MIP-1α, and MIP-1β, is also used when macrophage tropic (R5) HIV is infected ( Science, 272 , 1955 (1996);

Thus, those that can compete for HIV with CXCR4 or CCR5, or those that bind to the HIV virus and render the virus incapable of binding to CXCR4 or CCR5, could be HIV infection inhibitors. In some cases, low-molecular-weight compounds discovered as inhibitors of HIV infection have been shown to be actually antagonists of CXCR4 (Nature Medicine, 4 , 72 (1998); Non-Patent Document 10).

  From the above, it is considered that chemokines / chemokine receptors are deeply involved in inflammation, immune diseases or HIV infection. For example, various inflammatory diseases, asthma, atopic dermatitis, hives, allergic diseases (allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteropathy, etc.), nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis Treatment of psoriasis, rhinitis, conjunctivitis, ischemia-reperfusion injury, multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome, shock due to bacterial infection, diabetes, autoimmune diseases, transplant organ rejection, immunity It is thought to be involved in suppression, prevention of cancer metastasis, and acquired immunodeficiency syndrome.

（式中、Ａ^iZおよびＢ^jZはそれぞれ別個に炭素、窒素、酸素または硫黄から選ばれ（ただし、Ａ^iZの少なくとも１個の原子は炭素であり、かつ少なくとも１個のＢ^jZは炭素である。）；
Ａ^iZおよびＢ^jZによって形成されるスピロ二環は、それぞれ場合によって部分的に不飽和であってもよく、
ｐＺおよびｑＺはそれぞれ別個に２から６までの数であり、
ｍＺは０からｐＺまでの数であり、
Ｒ^10Zは同じかまたは異なっており、水素、アルキル、ハロ置換アルキル、アルケニル、アルキニル、シクロアルキル、＝Ｏ、＝Ｓ等からそれぞれ別個に選ばれる非干渉性置換基であり、
ｎＺは０からｑＺまでの数であり、
Ｒ^0Zは同じかまたは異なっており、水素、アルキル、ハロ置換アルキル、アルケニル、アルキニル、シクロアルキル、＝Ｏ、＝Ｓ等からそれぞれ別個に選ばれる非干渉性置換基であり、
−（Ｌ^Z）−は結合であるか、または炭素、窒素、硫黄および酸素から選ばれる１個から１０個の原子からなる二価の置換もしくは非置換鎖であり、
Ｑ^Zは１個または２個以上の塩基性ラジカルを含む塩基性基であり、かつ
Ｒ^3Zは１個または２個以上の酸性ラジカルを含む酸性基である。）で示される化合物が血小板凝集抑制に有用である旨の記載がある。 On the other hand, in the pamphlet of WO 97/11940 (Patent Document 1), the general formula (Z)

^Wherein A ^iZ and B ^jZ are each ^{independently} selected from carbon, nitrogen, oxygen or sulfur (provided that at least one atom of A ^iZ is carbon and at least one B ^jZ is carbon ));
The spiro bicycle formed by A ^iZ and B ^jZ may each be optionally partially unsaturated,
pZ and qZ are each independently a number from 2 to 6,
mZ is a number from 0 to pZ,
R ^10Z is the same or different and is a non-interfering substituent independently selected from hydrogen, alkyl, halo-substituted alkyl, alkenyl, alkynyl, cycloalkyl, ^{ＯO, ＳS} and the like;
nZ is a number from 0 to qZ;
R ^0Z is the same or different and is a non-interfering substituent independently selected from hydrogen, alkyl, halo-substituted alkyl, alkenyl, alkynyl, cycloalkyl, ^{ＯO, ＳS} and the like;
-(L ^Z )-is a bond or a divalent substituted or unsubstituted chain consisting of 1 to 10 atoms selected from carbon, nitrogen, sulfur and oxygen;
Q ^Z is a basic group containing one or more basic radicals, and R ^3Z is an acidic group containing one or more acidic radicals. )) Is useful for inhibiting platelet aggregation.

（式中、ｍＹまたはｌＹは、それぞれ独立して、０、１、２、３、４または５を表わし、
Ｒ^1Yは、水素原子、Ｃ１〜８アルキル基、Ｃ２〜８アルケニル基、Ｃ２〜８アルキニル基等を表わし、
Ｗ^Yは、単結合、Ｃ１〜３アルキル基、オキソ等で置換したＣ１〜３アルキル基等を表わし、
Ｑ^Yは、−ＮＲ²−、−Ｏ−、−Ｓ−、−Ｓ（Ｏ）−または−ＳＯ₂−を表わし、
Ｘ^Yは、単結合、Ｃ１〜３アルキル基、オキソ等で置換したＣ１〜３アルキル基等を表わし、
Ｙ^Y−Ｚ^Y環は、フェニル、ナフチル、ヘテロアリールを表わす。ただし、各記号の定義は、一部を抜粋したものである。）で示される化合物がケモカイン受容体モジュレーターとして有用である旨の記載がある。 In addition, WO 98/25605 pamphlet (Patent Document 2) includes a compound represented by general formula (Y)

(Wherein, mY or 1Y each independently represents 0, 1, 2, 3, 4 or 5;
R ^1Y represents a hydrogen atom, a C1-8 alkyl group, a C2-8 alkenyl group, a C2-8 alkynyl group, or the like;
W ^Y represents a single bond, a C1-3 alkyl group, a C1-3 alkyl group substituted with oxo or the like,
Q ^{Y is, -NR 2 -, - O -} , - S -, - S (O) - or -SO ₂ - represents,
^XY represents a single bond, a C1-3 alkyl group, a C1-3 alkyl group substituted with oxo or the like,
The Y ^Y -Z ^Y ring represents phenyl, naphthyl or heteroaryl. However, the definition of each symbol is partly excerpted. ) Is useful as a chemokine receptor modulator.

J. Exp. Med., 189 (3), 451 (1999) J. Clin. Invest., 102, 1933 (1998) J. Immunology, 163, 403 (1999) Kidney Int., 51, 770 (1997) Cell, 52, 631 (1985) Science, 272, 872 (1996) Nature, 382, 829 (1996) Nature, 382, 833 (1996) Science, 272, 1955 (1996) Nature Medicine, 4, 72 (1998) WO 97/11940 pamphlet WO 98/25605 pamphlet

  The present inventors have conducted intensive studies to find compounds that control the actions of various chemokines / chemokine receptors. As a result, the triazaspiro [5.5] undecane derivative represented by the general formula (I) was The inventors have found that the object has been achieved and completed the present invention.

［式中、Ｒ¹は、下記式（１）または（２）で示される基：

（基中、Ｇは、単結合、Ｃ１〜４アルキレン基、Ｃ２〜４アルケニレン基、または−ＣＯ−を表わし、
Ａ環は、(1)Ｃ５〜１０の単環または二環式炭素環、または(2)１〜２個の窒素原子および／または１〜２個の酸素原子を含む５〜１０員の単環または二環式複素環を表わし、
Ｒ⁶は、
（１）Ｃ１〜４アルキル基、
（２）ハロゲン原子、
（３）ニトリル基、
（４）トリフルオロメチル基、
（５）−ＯＲ⁸基、
（６）−ＳＲ⁹基、
（７）−ＮＲ¹⁰Ｒ¹¹基、
（８）−ＣＯＯＲ¹²基、
（９）−ＣＯＮＲ¹³Ｒ¹⁴基、
（１０）−ＳＯ₂ＮＲ¹⁵Ｒ¹⁶基、
（１１）−ＮＲ¹⁷ＳＯ₂Ｒ¹⁸基、
（１２）−Ｓ（Ｏ）Ｒ¹⁹基、
（１３）−ＳＯ₂Ｒ²⁰基、
（１４）−Ｎ（ＳＯ₂Ｒ²¹）₂基、
（１５）(a)−ＯＲ⁸基、(b)−ＮＲ¹⁰Ｒ¹¹基および(c)Ｃｙｃ１から選択される１個の基によって置換されたＣ１〜４アルキル基、または
（１６）−ＮＲ²⁷ＣＯＲ²⁸基を表わし、
Ｒ⁸〜Ｒ¹⁷は、それぞれ独立して、(1)水素原子、(2)Ｃ１〜４アルキル基、(3)Ｃｙｃ１、(4)−ＯＲ²²基、または(5)(a)−ＯＲ²²基、(b)−ＮＲ²³Ｒ²⁴基、(c)−ＣＯＯＲ²⁵基および(d)Ｃｙｃ１から任意に選ばれる１個の基に置換されたＣ１〜４アルキル基を表わすか、
Ｒ¹⁰とＲ¹¹、Ｒ¹³とＲ¹⁴、Ｒ¹⁵とＲ¹⁶は、それぞれが結合する窒素原子と一緒になって、１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わし（ただし、該複素環は、Ｃ１〜４アルキル基または水酸基で置換されていてもよい。）、
Ｒ²²〜Ｒ²⁵は、それぞれ独立して、(1)水素原子、(2)Ｃ１〜４アルキル基、または(3)Ｃ１〜４アルコキシ基が置換したＣ１〜４アルキル基を表わすか、
Ｒ²³とＲ²⁴は、結合する窒素原子と一緒になって、１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わし（ただし、該複素環は、Ｃ１〜４アルキル基または水酸基で置換されていてもよい。）、
Ｒ¹⁸〜Ｒ²¹は、それぞれ独立して、Ｃ１〜４アルキル基を表わし、
Ｒ²⁷は、(1)水素原子、(2)Ｃ１〜４アルキル基、(3)Ｃｙｃ１または(4)(a)−ＯＲ²²基、(b)−ＮＲ²³Ｒ²⁴基、(c)−ＣＯＯＲ²⁵基および(d)Ｃｙｃ１から任意に選ばれる１個の基によって置換されたＣ１〜４アルキル基を表わし、
Ｒ²⁸は、(1)Ｃ１〜４アルキル基、(2)Ｃｙｃ１または(3)(a)−ＯＲ²²基、(b)−ＮＲ²³Ｒ²⁴基、(c)−ＣＯＯＲ²⁵基および(d)Ｃｙｃ１から任意に選ばれる一個の基によって置換されたＣ１〜４アルキル基を表わし、
Ｃｙｃ１は(1)Ｃ５〜６の単環炭素環または(2)１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わし（ただし、該炭素環または複素環は、Ｃ１〜４アルコキシ基、ハロゲン原子または−ＣＯＯＲ²⁹基（Ｒ²⁹は、(1)水素原子、(2)Ｃ１〜４アルキル基、(3)Ｃｙｃ１または(4)(a)−ＯＲ²²基、(b)−ＮＲ²³Ｒ²⁴基、(c)−ＣＯＯＲ²⁵基および(d)Ｃｙｃ１から任意に選ばれる一個の基によって置換されたＣ１〜４アルキル基を表わす。）で置換されていてもよい。）、
Ｅは、単結合、−Ｏ−、−Ｓ−、−ＣＯ−、または−ＣＨＯＨ−を表わし、
Ｂ環は、(1)Ｃ５〜６の単環炭素環または(2)１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わし、
Ｒ⁷は、Ｃ１〜４アルキル基またはハロゲン原子を表わし、
ｎは、０または１〜４の整数を表わし、
ｍは、０または１〜４の整数を表わす。）を表わし、
Ｒ²は、
（１）Ｃ１〜４アルキル基、
（２）Ｃ２〜４アルキニル基、または
（３）(a)−ＯＲ³⁰基、(b)−ＮＲ³¹Ｒ³²基および(c)Ｃｙｃ３から選択される１個の基によって置換されたＣ１〜４アルキル基（基中、Ｒ³⁰〜Ｒ³²は、それぞれ独立して、(1)水素原子、(2)Ｃ１〜４アルキル基、(3)Ｃｙｃ３または(4)Ｃｙｃ３によって置換されたＣ１〜４アルキル基を表わし、Ｃｙｃ３は、(1)Ｃ５〜６の単環炭素環または(2)１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わす（ただし、該炭素環または複素環は、Ｃ１〜４アルコキシ基で置換されていてもよい。）。）を表わし、
Ｒ³およびＲ⁴は、それぞれ独立して、
（１）水素原子、
（２）Ｃ１〜４アルキル基、または
（３）(a)Ｃｙｃ２および(b)水酸基から任意に選択される１〜２個の基によって置換されたＣ１〜４アルキル基
（基中、Ｃｙｃ２は、(1)Ｃ５〜６の単環炭素環または(2)１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員の単環複素環を表わす。）を表わすか、
Ｒ³とＲ⁴は、一緒になって、

（基中、Ｒ²⁶はＣ１〜４アルキル基またはＣｙｃ２を表わす。）を表わし、
Ｒ⁵は、水素原子またはＣ１〜４アルキル基を表わす。］
で示されるトリアザスピロ［５．５］ウンデカン誘導体化合物、それらの四級アンモニウム塩、それらのＮ−オキシド、またはそれらの非毒性塩（ただし、（３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン・塩酸塩を表わさないものとする。）。
［２］Ｒ³およびＲ⁴が水素原子である前記［１］記載の化合物、その四級アンモニウム塩、そのＮ−オキシド、またはその非毒性塩。
［３］Ｒ³が水素原子であり、Ｒ⁴が
（１）Ｃ１〜４アルキル基、または
（２）(a)Ｃｙｃ２および(b)水酸基から任意に選択される１〜２個の基によって置換されたＣ１〜４アルキル基である前記［１］記載の化合物、その四級アンモニウム塩、そのＮ−オキシド、またはその非毒性塩。
［４］Ｒ³およびＲ⁴がそれぞれ独立して、
（１）Ｃ１〜４アルキル基、または
（２）(a)Ｃｙｃ２および(b)水酸基から任意に選択される１〜２個の基によって置換されたＣ１〜４アルキル基である前記［１］記載の化合物、その四級アンモニウム塩、そのＮ−オキシド、またはその非毒性塩。
［５］Ｒ³とＲ⁴が一緒になって、

（式中、Ｒ²⁶は前記１記載と同じ意味を表わす。）を表わす前記［１］記載の化合物、その四級アンモニウム塩、そのＮ−オキシド、またはその非毒性塩。
［６］化合物が
(1) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−ベンジル−１，４，９−トリアザスピロ［５．５］ウンデカン、
(2) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（６−フェニルオキシピリジン−３−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(3) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メトキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(4) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（３−メトキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(5) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−フルオロフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(6) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−クロロフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(7) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（フェニルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(8) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（１−フェニル−１−ヒドロキシメチル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(9) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−（モルホリン−４−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(10) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（６−メチルピリジン−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(11) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（ピリジン−１−オキシド−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(12) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−ヒドロキシピペリジン−１−イルメチル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(13) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(14) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（１，３，５−トリメチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(15) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−アミノスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(16) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルチオフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(17) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(18) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−シアノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(19) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（フェニルチオ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(20) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−ヒドロキシフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(21) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メチルスルホニルアミノフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(22) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(23) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(24) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（６−メチルピリジン−１−オキシド−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(25) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−ヒドロキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(26) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（６−（４−メトキシフェニルオキシ）ピリジン−３−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(27) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（メチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(28) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ−メチル−Ｎ−（２−ヒドロキシエチル）アミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(29) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(30) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(31) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−（モルホリン−４−イル）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(32) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(33) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルスルフィニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(34) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(35) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(36) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−アミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(37) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(38) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メチルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(39) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジエチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(40) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（４−メチルピペラジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(41) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（５−クロロ−３−メチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(42) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(43) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(44) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(45) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（ピリジン−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(46) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(47) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(48) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（２，４−ジフルオロフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(49) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（ピリジン−２−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(50) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メチルアミノカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(51) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−シクロヘキシルオキシフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(52) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（３，４，５，６−テトラヒドロピラン−４−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(53) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メトキシフェニルメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(54) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（シクロヘキシルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(55) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−（ピロリジン−１−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(56) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−フルオロフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(57) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−フェニルエチル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(58) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（１−ベンジルオキシカルボニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(59) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−（２−ヒドロキシエチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(60) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−（１−メチルスルホニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(61) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−ヒドロキシメチルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(62) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（（１Ｓ）−１−ヒドロキシ−２−メチルプロピル）−９−（６−フェニルオキシピリジン−３−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(63) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(64) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(65) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(66) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−メチルスルホニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(67) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−メチルスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(68) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−（モルホリン−４−イル）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(69) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（４−メチルピペラジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(70) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−メチルスルフィニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(71) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（ピリジン−１−オキシド−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(72) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(73) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−（モルホリン−４−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(74) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジエチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(75) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−（２−ヒドロキシエチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(76) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−（ピロリジン−１−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(77) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（シクロヘキシルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(78) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（３−メトキシプロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(79) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−メチルスルフィニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(80) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−プロピルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(81) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−エチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(82) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−シクロペンチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(83) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（１，１−ジメチルエチル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(84) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（１−ベンジルオキシカルボニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(85) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（（４−メトキシフェニル）メチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(86) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（３−メトキシプロピルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(87) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メトキシカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(88) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メトキシフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(89) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（３−（モルホリン−４−イル）プロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(90) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（ピロリジン−１−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(91) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（ピペリジン−１−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(92) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（モルホリン−４−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(93) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（Ｎ−メチル−Ｎ−（２−（ピリジン−２−イル）エチル）アミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(94) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（シクロヘキシルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(95) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（Ｎ，Ｎ−ジメチルアミノスルホニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(96) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−メトキシカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(97) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（１−メチルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(98) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（１−メチルスルホニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(99) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（３−（Ｎ，Ｎ−ジメチルアミノ）プロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(100) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−（Ｎ，Ｎ−ジメチルアミノ）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(101) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（Ｎ−メチル−Ｎ−（２−（Ｎ’，Ｎ’−ジメチルアミノ）エチル）アミノスルホニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(102) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−（（Ｎ，Ｎ−ジメチルアミノ）メチル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(103) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(104) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−メチルアミノカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(105) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（（メトキシカルボニル）メチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(106) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３−（３，５−ジメチル−１−フェニルピラゾール−４−イル）−２Ｅ−プロペニル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(107) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（カルボキシメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(108) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３−（３，５−ジメチル−１−フェニルピラゾール−４−イル）プロピル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(109) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(110) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(111) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(112) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(113) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−（モルホリン−４−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(114) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−メチルスルホニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(115) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−メチルスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(116) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（２−（モルホリン−４−イル）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(117) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（４−メチルピペラジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(118) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−メチルスルフィニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(119) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(120) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−（２−ヒドロキシエチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(121) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−（ピロリジン−１−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(122) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（シクロヘキシルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(123) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（３−メトキシプロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(124) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−メチルスルフィニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(125) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−プロピルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(126) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−エチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(127) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−シクロペンチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(128) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（３−（モルホリン−４−イル）プロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(129) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（Ｎ，Ｎ−ジメチルアミノスルホニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(130) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（ピロリジン−１−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(131) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−（Ｎ，Ｎ−ジメチルアミノ）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(132) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（シクロヘキシルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(133) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−メトキシカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(134) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（３−メトキシプロピルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(135) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（Ｎ−メチル−Ｎ−（２−（ピリジン−２−イル）エチル）アミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(136) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（（４−メトキシフェニル）メチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(137) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−メトキシカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(138) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−メトキシフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(139) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（１−メチルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(140) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（１−メチルスルホニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(141) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（３−（Ｎ，Ｎ−ジメチルアミノ）プロピルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(142) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−（Ｎ−メチル−Ｎ−（２−（Ｎ’，Ｎ’−ジメチルアミノ）エチル）アミノスルホニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(143) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（ピペリジン−１−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(144) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（モルホリン−４−イルカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(145) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−（（Ｎ，Ｎ−ジメチルアミノ）メチル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(146) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（４−メチルアミノカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(147) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（１，１−ジメチルエチル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(148) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−（１−ベンジルオキシカルボニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(149) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−ヒドロキシメチルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(150) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（（メトキシカルボニル）メチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(151) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（カルボキシメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(152) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−フェニルオキシフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(153) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（６−フェニルオキシピリジン−３−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(154) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−フルオロフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(155) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−クロロフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(156) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−シアノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(157) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(158) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（６−メチルピリジン−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(159) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（１−メチルエチル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(160) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルスルフィルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(161) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（３，４，５，６−テトラヒドロピラン−４−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(162) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−フェニルカルボニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(163) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（１−フェニル−１−ヒドロキシメチル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(164) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(165) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−メチルアミノスルホニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(166) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（Ｎ−メチル−Ｎ−（２−ヒドロキシエチル）アミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(167) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（ピリジン−２−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(168) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(169) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（１，３，５−トリメチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(170) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(171) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（Ｎ，Ｎ−ビスメチルスルホニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(172) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−メチルスルホニルアミノフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(173) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(174) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(175) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（モルホリン−４−イルカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(176) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−アミノカルボニルフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(177) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−アミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(178) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−アミノスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(179) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（６−メチルピリジン−１−オキシド−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(180) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−ヒドロキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(181) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−ヒドロキシフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(182) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(183) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（ピロリジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(184) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（５−クロロ−３−メチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(185) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メトキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(186) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（３−メトキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(187) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(188) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(189) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−メチルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(190) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−フルオロフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(191) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（６−（４−メトキシフェニルオキシ）ピリジン−３−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(192) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルスルホニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(193) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(194) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（２−ヒドロキシエチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(195) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(196) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（２−（モルホリン−４−イル）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(197) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−（モルホリン−４−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(198) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（１，４−ベンゾジオキサン−６−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(199) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジエチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(200) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（ピリジン−１−オキシド−３−イルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(201) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（４−メチルピペラジン−１−イルスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(202) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(203) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（２，４−ジフルオロフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(204) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(205) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−メチルアミノカルボニルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(206) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(207) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（（４−メトキシフェニル）メチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(208) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（３−メトキシプロピルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(209) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（Ｎ−メチル−Ｎ−（２−（ピリジン−２−イル）エチル）アミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(210) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−（ピロリジン−１−イルカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(211) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−クロロフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(212) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−トリフルオロメチルフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(213) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−メトキシフェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(214) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−エチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(215) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−プロピルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(216) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（１，１−ジメチルエチル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(217) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−シクロペンチルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(218) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（２−フェニルエチル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(219) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（１−ベンジルオキシカルボニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(220) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（シクロヘキシルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(221) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（１−メチルスルホニルピペリジン−４−イル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(222) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−（２−ヒドロキシエチルアミノカルボニル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(223) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−ヒドロキシメチルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(224) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（（１Ｓ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(225) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（３，５−ジメチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(226) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(227) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（４−（４−（４−メトキシフェニルメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(228) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(229) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(230) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−（３，４，５，６−テトラヒドロピラン−４−イル）メチル）−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(231) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロペンチルメチル）−９−（３，５−ジメチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(232) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロペンチルメチル）−９−（４−（４−（４−メトキシフェニルメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(233) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロペンチルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(234) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロペンチルメチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(235) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(236) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(237) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−２−メチルプロピル）−９−（４−（４−メトキシフェニルメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(238) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(239) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(240) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メトキシフェニルメチルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(241) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−（４−（Ｎ，Ｎ−ジメチルアミノカルボニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(242) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(243) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メトキシカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(244) （３Ｒ）−１−プロピル−２，５−ジオキソ−３−（１−シクロヘキシルメチリデン）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(245) （３Ｓ）−１−プロピル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(246) （３Ｓ）−１−プロピル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(247) （３Ｓ）−１−プロピル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（３，５−ジメチル−１−（４−（２−（Ｎ，Ｎ−ジメチルアミノ）エチルアミノスルホニル）フェニル）ピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(248) （３Ｓ）−１−プロピル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(249) （３Ｓ）−１−プロピル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(250) １−ブチル−２，５−ジオキソ−９−（４−（４−メチルスルホニルアミノフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(251) １−ブチル−２，５−ジオキソ−９−（３，５−ジメチル−１−シクロヘキシルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(252) （３Ｒ）−１−（２−ブチニル）−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(253) （３Ｓ）−１−（２−ブチニル）−２，５−ジオキソ−３−（（１Ｓ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（３，５−ジメチル−１−フェニルピラゾール−４−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(254) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（２−（４−フェニルオキシフェニル）エチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(255) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（２−（４−フェニルオキシフェニル）エチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(256) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（２−メチルプロピル）−９−（２−（４−メトキシフェニル）エチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(257) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−エトキシカルボニルフェニル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(258) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−４−メチル−９−（４−フェニルオキシフェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(259) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（２−メチルプロパノイルアミノ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(260) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（２−メトキシアセチルアミノ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(261) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（２−フェニルアセチルアミノ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(262) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（２−（４−フルオロフェニル）アセチルアミノ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(263) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メトキシカルボニルフェニルアミノカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(264) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メトキシフェニルメチルオキシカルボニル）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(265) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（２−（４−メチルアミノカルボニルフェニルオキシ）ピリジン−５−イルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(266) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（（１Ｓ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(267) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（ピリジン−３−イルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(268) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−フェニルメチル−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(269) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（ピリジン−２−イルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(270) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−ヒドロキシメチル−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(271) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（ピリジン−１−オキシド−２−イルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(272) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（ピリジン−１−オキシド−３−イルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(273) （３Ｒ）−１−（４−メトキシフェニルメチル）−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(274) （３Ｒ）−１−フェニルメチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(275) （３Ｒ）−１−（２−メトキシエチル）−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(276) （３Ｒ）−１−（ピリジン−２−イルメチル）−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(277) （３Ｒ）−１−（ピリジン−３−イルメチル）−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(278) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−シクロヘキシルメチル−９−（４−（４−カルボキシフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(279) （３Ｓ）−１−ブチル−２，５−ジオキソ−３−（ピリジン−１−オキシド−２−イルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン・９−オキシド、
(280) １−ブチル−２，５−ジオキソ−３−（モルホリン−４−イルメチル）９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(281) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−（Ｎ−ヒドロキシカルバモイル）フェニルオキシ）フェニルメチル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(282) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルカルボニル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
(283) （３Ｒ）−１−ブチル−２，５−ジオキソ−３−（（１Ｒ）−１−ヒドロキシ−１−シクロヘキシルメチル）−９−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニル）−１，４，９−トリアザスピロ［５．５］ウンデカン、
それらの四級アンモニウム塩、それらのＮ−オキシド、またはそれらの非毒性塩である前記［１］記載の化合物。
［７］前記［１］に記載の一般式（Ｉ）で示されるトリアザスピロ［５．５］ウンデカン誘導体化合物、それらの四級アンモニウム塩、それらのＮ−オキシド、またはそれらの非毒性塩を有効成分として含有する医薬組成物。
［８］前記［１］に記載の一般式（Ｉ）で示されるトリアザスピロ［５．５］ウンデカン誘導体化合物、それらの四級アンモニウム塩、それらのＮ−オキシド、またはそれらの非毒性塩を有効成分として含有するケモカイン／ケモカイン受容体の作用の制御剤。
［９］前記［１］に記載の一般式（Ｉ）で示されるトリアザスピロ［５．５］ウンデカン誘導体化合物、それらの四級アンモニウム塩、それらのＮ−オキシド、またはそれらの非毒性塩を有効成分として含有する喘息、アトピー性皮膚炎、蕁麻疹、アレルギー性気管支肺アスペルギルス症、アレルギー性好酸球性胃腸症、腎炎、腎症、肝炎、関節炎、慢性関節リウマチ、乾癬、鼻炎、結膜炎、虚血再灌流傷害の抑制、多発性硬化症、潰瘍性大腸炎、急性呼吸窮迫症候群、細菌感染に伴うショック、糖尿病、自己免疫疾患の治療、移植臓器拒絶反応、免疫抑制、癌転移予防、後天性免疫不全症候群の予防および／または治療剤。 That is, the present invention relates to the following derivative compounds and uses thereof.
[1] General formula (I)

[Wherein, R ¹ Is a group represented by the following formula (1) or (2):

(In the group, G represents a single bond, a C1-4 alkylene group, a C2-4 alkenylene group, or -CO-,
Ring A is (1) a C5-10 monocyclic or bicyclic carbocyclic ring, or (2) a 5-10 membered monocyclic ring containing 1-2 nitrogen atoms and / or 1-2 oxygen atoms. Or represents a bicyclic heterocycle,
R ⁶ Is
(1) a C1-4 alkyl group,
(2) a halogen atom,
(3) a nitrile group,
(4) trifluoromethyl group,
(5) -OR ⁸ Group,
(6) -SR ⁹ Group,
(7) -NR ^Ten R ¹¹ Group,
(8) -COOR ¹² Group,
(9) -CONR ¹³ R ¹⁴ Group,
(10) -SO _Two NR ^Fifteen R ¹⁶ Group,
(11) -NR ¹⁷ SO _Two R ¹⁸ Group,
(12) -S (O) R ¹⁹ Group,
(13) -SO _Two R ²⁰ Group,
(14) -N (SO _Two R ^{twenty one} ) _Two Group,
(15) (a) -OR ⁸ Group, (b) -NR ^Ten R ¹¹ A C 1-4 alkyl group substituted by a group and (c) one group selected from Cyc1, or
(16) -NR ²⁷ COR ²⁸ Represents a group,
R ⁸ ~ R ¹⁷ Each independently represents (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) Cyc1, (4) -OR ^{twenty two} Group, or (5) (a) -OR ^{twenty two} Group, (b) -NR ^{twenty three} R ^{twenty four} Group, (c) -COOR ^{twenty five} A group and (d) a C1-4 alkyl group substituted by one group arbitrarily selected from Cyc1,
R ^Ten And R ¹¹ , R ¹³ And R ¹⁴ , R ^Fifteen And R ¹⁶ Represents a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom together with the nitrogen atom to which each is bonded (provided that the heterocycle is It may be substituted by a C1-4 alkyl group or a hydroxyl group.),
R ^{twenty two} ~ R ^{twenty five} Each independently represents (1) a hydrogen atom, (2) a C1-4 alkyl group, or (3) a C1-4 alkyl group substituted with a C1-4 alkoxy group,
R ^{twenty three} And R ^{twenty four} Represents a 5- to 6-membered monocyclic heterocyclic ring containing 1 to 2 nitrogen atoms and / or 1 oxygen atom together with the nitrogen atom to be bonded (provided that the heterocyclic ring is May be substituted with a 4-alkyl group or a hydroxyl group.),
R ¹⁸ ~ R ^{twenty one} Each independently represents a C1-4 alkyl group;
R ²⁷ Represents (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) Cyc1 or (4) (a) -OR ^{twenty two} Group, (b) -NR ^{twenty three} R ^{twenty four} Group, (c) -COOR ^{twenty five} A group and (d) a C1-4 alkyl group substituted by one group arbitrarily selected from Cyc1,
R ²⁸ Is (1) a C1-4 alkyl group, (2) Cyc1 or (3) (a) -OR ^{twenty two} Group, (b) -NR ^{twenty three} R ^{twenty four} Group, (c) -COOR ^{twenty five} A group and (d) a C1-4 alkyl group substituted by one group arbitrarily selected from Cyc1,
Cyc1 represents (1) a C5-6 monocyclic carbocycle or (2) a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom (provided that the carbon The ring or heterocycle is a C1-4 alkoxy group, a halogen atom or ²⁹ Group (R ²⁹ Represents (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) Cyc1 or (4) (a) -OR ^{twenty two} Group, (b) -NR ^{twenty three} R ^{twenty four} Group, (c) -COOR ^{twenty five} And (d) a C1-4 alkyl group substituted by one group arbitrarily selected from Cyc1. ) May be substituted. ),
E represents a single bond, -O-, -S-, -CO-, or -CHOH-,
Ring B represents (1) a C5-6 monocyclic carbocyclic ring or (2) a 5- to 6-membered monocyclic heterocyclic ring containing 1-2 nitrogen atoms and / or one oxygen atom,
R ⁷ Represents a C1-4 alkyl group or a halogen atom,
n represents 0 or an integer of 1 to 4,
m represents 0 or an integer of 1 to 4. )
R ^Two Is
(1) a C1-4 alkyl group,
(2) a C2-4 alkynyl group, or
(3) (a) -OR ³⁰ Group, (b) -NR ³¹ R ³² Group and (c) a C1-4 alkyl group substituted by one group selected from Cyc3 (in the group, R ³⁰ ~ R ³² Each independently represents (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkyl group substituted by Cyc3 or (4) Cyc3, and Cyc3 is represented by (1) C5 -6 monocyclic carbocycles or (2) a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom (provided that the carbocycle or heterocycle is And may be substituted with a C1-4 alkoxy group.). )
R ^Three And R ^Four Are, independently of each other,
(1) a hydrogen atom,
(2) a C1-4 alkyl group, or
(3) a C1-4 alkyl group substituted by one or two groups arbitrarily selected from (a) Cyc2 and (b) a hydroxyl group
(In the group, Cyc2 represents (1) a C5-6 monocyclic carbocycle or (2) a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom. )) Or
R ^Three And R ^Four Together

(In the group, R ²⁶ Represents a C1-4 alkyl group or Cyc2. )
R ^Five Represents a hydrogen atom or a C1-4 alkyl group. ]
, A quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof (provided that (3R) -1-butyl-2,5-dioxo-3) Represents-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride. Make it not exist.).
[2] R ^Three And R ^Four Is a hydrogen atom, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof.
[3] R ^Three Is a hydrogen atom, and R ^Four But
(1) a C1-4 alkyl group, or
(2) The compound according to the above [1], which is a C1-4 alkyl group substituted by one or two groups arbitrarily selected from (a) Cyc2 and (b) a hydroxyl group, a quaternary ammonium salt thereof, N-oxide or a non-toxic salt thereof.
[4] R ^Three And R ^Four Are independent of each other,
(1) a C1-4 alkyl group, or
(2) The compound according to the above [1], which is a C1-4 alkyl group substituted by one or two groups arbitrarily selected from (a) Cyc2 and (b) a hydroxyl group, a quaternary ammonium salt thereof, N-oxide or a non-toxic salt thereof.
[5] R ^Three And R ^Four Together

(Where R ²⁶ Has the same meaning as described in 1 above. ) The compound according to the above [1], a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof.
[6] The compound
(1) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9-benzyl-1,4,9-triazaspiro [5.5] Undecane,
(2) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(3) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(4) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(5) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-fluorophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(6) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(7) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylcarbonyl) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane,
(8) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(9) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(10) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridin-3-yloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(11) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(12) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxypiperidin-1-ylmethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(13) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(14) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(15) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(16) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylthiophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(17) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(18) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-cyanophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(19) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylthio) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane,
(20) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(21) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylsulfonyl) Aminophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(22) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(23) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(24) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridine-1-oxide-3 -Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(25) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(26) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6- (4-methoxyphenyloxy) pyridine-3- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(27) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (methyl Aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(28) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N -Methyl-N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(29) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(30) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(31) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -(Morpholin-4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(32) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(33) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(34) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(35) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(36) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(37) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(38) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(39) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(40) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4 -Methylpiperazin-1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(41) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (5-chloro-3-methyl-1-phenylpyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(42) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(43) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(44) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2- (N, N- Dimethylamino) ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(45) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-3-yloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(46) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(47) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(48) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (2,4- Difluorophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(49) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (pyridine-2- Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(50) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylamino Carbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(51) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4-cyclohexyloxyphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(52) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3,4,5,6-tetrahydropyran -4-yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(53) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(54) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(55) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(56) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(57) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Phenylethyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(58) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxy Carbonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(59) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(60) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonyl) Piperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(61) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(62) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(63) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(64) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(65) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(66) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(67) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(68) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) Ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(69) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(70) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(71) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) phenylmethyl) -1,4, 9-triazaspiro [5.5] undecane,
(72) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(73) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(74) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-diethylaminosulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(75) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(76) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(77) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(78) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(79) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(80) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(81) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(82) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(83) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(84) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(85) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane,
(86) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(87) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(88) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(89) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) Propylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(90) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(91) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(92) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(93) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) Aminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(94) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(95) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(96) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(97) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(98) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(99) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) )) Propylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(100) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(101) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′, N′-dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(102) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(103) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane,
(104) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(105) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(106) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) -2E- Propenyl) -1,4,9-triazaspiro [5.5] undecane;
(107) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(108) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) propyl)- 1,4,9-triazaspiro [5.5] undecane,
(109) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(110) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(111) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(112) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) ethylaminocarbonyl )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(113) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(114) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(115) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(116) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) ethylaminosulfonyl) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(117) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) phenyl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(118) (3S) -1-Butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(119) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(120) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(121) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(122) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(123) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(124) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(125) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(126) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(127) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(128) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) propylaminosulfonyl) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(129) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(130) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(131) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(132) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(133) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane,
(134) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(135) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) aminocarbonyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(136) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane,
(137) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(138) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl) -1,4, 9-triazaspiro [5.5] undecane,
(139) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(140) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(141) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) propylaminosulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(142) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′, N′-dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(143) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(144) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(145) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(146) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(147) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(148) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(149) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(150) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(151) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(152) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenyloxyphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(153) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(154) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-fluorophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(155) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(156) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-cyanophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(157) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(158) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridin-3-yloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(159) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-methylethyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(160) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(161) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3,4,5,6-tetrahydropyran -4-yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(162) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenylcarbonylphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(163) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(164) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(165) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylamino) Sulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(166) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N -Methyl-N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(167) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (pyridine-2- Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(168) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(169) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(170) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(171) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-bismethylsulfonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(172) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylsulfonyl) Aminophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(173) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(174) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(175) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(176) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-aminocarbonylphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(177) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(178) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(179) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridine-1-oxide-3) -Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(180) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(181) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(182) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(183) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(184) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (5-chloro-3-methyl-1-phenylpyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(185) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(186) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(187) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-dimethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(188) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(189) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(190) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(191) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6- (4-methoxyphenyloxy) pyridine-3- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(192) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(193) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2- (N, N- Dimethylamino) ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(194) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(195) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(196) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(Morpholin-4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(197) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (morpholin-4-ylcarbonyl)) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(198) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,4-benzodioxan-6-ylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(199) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(200) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (pyridine-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(201) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (4 -Methylpiperazin-1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(202) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(203) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2,4- Difluorophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(204) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(205) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylamino) Carbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(206) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(207) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(208) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(209) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N-methyl-N- (2- ( Pyridin-2-yl) ethyl) aminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(210) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(211) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-chlorophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(212) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-trifluoro Methylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(213) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(214) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-ethylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(215) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-propylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(216) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1,1- Dimethylethyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(217) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclopentylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(218) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2-phenylethyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(219) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-benzyloxy Carbonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(220) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(221) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-methylsulfonyl) Piperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(222) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(223) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(224) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(225) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(226) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(227) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(228) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(229) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(230) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(231) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(232) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4- (4-methoxyphenylmethylaminocarbonyl) ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(233) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(234) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(235) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(236) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(237) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(238) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(239) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(240) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(241) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(242) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(243) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(244) (3R) -1-propyl-2,5-dioxo-3- (1-cyclohexylmethylidene) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(245) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(246) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(247) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) )) Ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(248) (3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(249) (3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(250) 1-butyl-2,5-dioxo-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(251) 1-butyl-2,5-dioxo-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(252) (3R) -1- (2-butynyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenyl Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(253) (3S) -1- (2-butynyl) -2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenyl Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(254) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5.5] undecane ,
(255) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5 .5] undecane,
(256) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-methoxyphenyl) ethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(257) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-ethoxycarbonylphenyl) -1,4,9-triazaspiro [5.5] undecane,
(258) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-4-methyl-9- (4-phenyloxyphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(259) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methylpropanoylamino) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(260) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methoxyacetylamino) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(261) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-phenylacetylamino) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(262) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2- (4-fluorophenyl) acetylamino ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(263) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(264) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethyloxycarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(265) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (2- (4-methylaminocarbonylphenyloxy) pyridine- 5-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(266) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(267) (3S) -1-butyl-2,5-dioxo-3- (pyridin-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(268) (3S) -1-butyl-2,5-dioxo-3-phenylmethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(269) (3S) -1-butyl-2,5-dioxo-3- (pyridin-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(270) (3S) -1-butyl-2,5-dioxo-3-hydroxymethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(271) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(272) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(273) (3R) -1- (4-methoxyphenylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(274) (3R) -1-phenylmethyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(275) (3R) -1- (2-methoxyethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonyl Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(276) (3R) -1- (pyridin-2-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(277) (3R) -1- (pyridin-3-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(278) (3R) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(279) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane-9-oxide,
(280) 1-butyl-2,5-dioxo-3- (morpholin-4-ylmethyl) 9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(281) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (N-hydroxycarbamoyl) phenyloxy ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(282) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylcarbonyl ) -1,4,9-Triazaspiro [5.5] undecane;
(283) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenyl) -1,4,9-triazaspiro [5.5] undecane,
The compound according to the above [1], which is a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof.
[7] An active ingredient comprising the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) according to the above [1], a quaternary ammonium salt thereof, an N-oxide thereof or a non-toxic salt thereof. A pharmaceutical composition containing
[8] An active ingredient comprising the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) according to the above [1], a quaternary ammonium salt thereof, an N-oxide thereof or a non-toxic salt thereof. An agent for controlling the action of a chemokine / chemokine receptor.
[9] An active ingredient comprising the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) described in the above [1], a quaternary ammonium salt thereof, an N-oxide thereof or a non-toxic salt thereof. Asthma, atopic dermatitis, hives, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteropathy, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, ischemia Suppression of reperfusion injury, multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome, shock due to bacterial infection, diabetes, treatment of autoimmune disease, transplant rejection, immunosuppression, prevention of cancer metastasis, acquired immunity An agent for preventing and / or treating insufficiency syndrome.

In the present invention, examples of the C1-4 alkyl group include a methyl, ethyl, propyl, butyl group and isomers thereof.
Examples of the C1-4 alkoxy group include methoxy, ethoxy, propoxy, butoxy and isomers thereof.

Examples of the halogen atom include chlorine, bromine, fluorine and iodine atoms.
Examples of the C1-4 alkylene group include a methylene, ethylene, trimethylene, tetramethylene group and isomers thereof.

Examples of the C2-4 alkenylene group include vinylene, propenylene, butenylene, and isomers thereof.
Examples of the C2-4 alkynyl group include an ethynyl, propynyl, butynyl group and isomer groups thereof.

  Examples of the C5-10 monocyclic or bicyclic carbocyclic ring include, for example, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene Benzene, indene, naphthalene, indane, tetrahydronaphthalene, bicyclo [3,3,0] octane, bicyclo [4,3,0] nonane, bicyclo [4,4,0] decane and the like.

  A 5- to 10-membered monocyclic or bicyclic heterocyclic ring containing 1 to 2 nitrogen atoms and / or 1 to 2 oxygen atoms means 1 to 2 nitrogen atoms and / or 1 to 2 It is a 5- to 10-membered monocyclic or bicyclic heterocyclic aryl containing an oxygen atom, or a part or the whole of which is saturated. For example, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepin, oxazole, isoxazole, furazane, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, indole, isoindole, Benzofuran, isobenzofuran, indazole, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, benzoxazole, benzimidazole, benzofurazan, benzotriazole, pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, dihydropyridine, tetrahydropyridine, Piperidine, dihydropyrazine, tetrohydropyrazine, Perazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine, tetrahydropyridazine, perhydropyridazine, dihydroazepine, tetrahydroazepine, perhydroazepine, dihydrodiazepine, tetrahydrodiazepine, perhydrodiazepine, dihydrofuran, tetrahydrofuran, Dihydropyran, tetrahydropyran, dihydrooxazole, tetrahydrooxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrooxadiazole, tetrahydrooxadiazole, tetrahydrooxadiazine, tetrahydrooxaazepine, tetrahydrooxadiazepine, perhydrooxaazepine, par Hydrooxadiazepine, morpholine, indoline, Soindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydroindazole, perhydroindazole, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline, dihydrophthalazine, tetrahydro Phthalazine, perhydrophthalazine, dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline, dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline , Dihydrobenzoxazole, par Examples include hydrobenzoxazole, dihydrobenzimidazole, perhydrobenzimidazole, dioxolan, dioxane, benzodioxalan, benzodioxane, and the like.

  A 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom, together with the nitrogen atom to which each is bound, refers to one or two nitrogen atoms and / or Alternatively, it is a 5- to 6-membered monocyclic heterocyclic aryl containing one oxygen atom, or a part or the whole of which is saturated. For example, pyrrole, imidazole, pyrazole, pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, dihydropyridine, tetrahydropyridine, piperidine, dihydropyrazine, tetrohydropyrazine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine, Examples include tetrahydropyridazine, perhydropyridazine, tetrahydrooxazole, tetrahydroisoxazole, dihydrooxadiazole, tetrahydrooxadiazole, tetrahydrooxadiazine, and morpholine ring.

  The C5-6 monocyclic carbocycle includes, for example, cyclopentane, cyclohexane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene ring and the like.

  A 5- to 6-membered monocyclic heterocycle containing 1 to 2 nitrogen atoms and / or 1 oxygen atom refers to a 5- to 6-membered heterocyclic ring containing 1 to 2 nitrogen atoms and / or 1 oxygen atom. Or a part or the whole thereof is saturated. For example, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, furan, pyran, oxazole, isoxazole, furazane, oxadiazole, oxazine, oxadiazine, pyrroline, pyrrolidine, imidazoline, imidazolidin, pyrazoline, pyrazolidine, dihydropyridine, Tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyrazine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine, tetrahydropyridazine, perhydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooxazole, tetrahydrooxazole , Dihydroisoxazole, tetrahydroi Oxazole, dihydro-oxadiazole, tetrahydro-oxadiazole, tetrahydropyran oxadiazine, morpholine ring and the like.

In the present invention, each of the groups represented by the groups R ¹ , R ² , R ³ , R ⁴ and R ⁵ is preferred. Particularly, those described in Examples are preferred.

  In the present invention, all isomers are included unless otherwise indicated. For example, the alkyl group, alkoxy group and alkylene group include straight-chain and branched ones. Further, isomers (E, Z, cis, trans) in double bonds, rings and condensed rings, isomers due to the presence of asymmetric carbon (R, S, α, β, enantiomers, diastereomers) , An optically active substance having optical activity (D, L, d, l-form), a polar form (high-polarity form, low-polarity form) by chromatographic separation, an equilibrium compound, a mixture of any ratio thereof, and a racemic mixture All are included in the present invention.

[salt]
In the present invention, all non-toxic salts are included. For example, common salts, acid addition salts and the like can be mentioned.
The compound of the present invention represented by the general formula (I) is converted into a corresponding salt by a known method. Non-toxic, water-soluble salts are preferred. Suitable salts include salts of alkali metals (eg, potassium, sodium, etc.), salts of alkaline earth metals (eg, calcium, magnesium, etc.), ammonium salts, and pharmaceutically acceptable organic amines (eg, tetramethylammonium, triethylamine, methylamine). Dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) amine, lysine, arginine, N-methyl-D-glucamine and the like.

  The compound of the present invention represented by the general formula (I) is converted into a corresponding acid addition salt by a known method. The acid addition salts are preferably non-toxic and water-soluble. Suitable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, or acetate, trifluoroacetate, lactate, tartrate, oxalate Like, fumarate, maleate, citrate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate Organic acid salts.

Further, the compound of the present invention represented by the general formula (I) or a salt thereof can be converted into a hydrate by a known method.
The compounds of the general formula (I) or their non-toxic salts are all preferred. Specific examples include the compounds described in the examples or non-toxic salts thereof.

The quaternary ammonium salt of the compound represented by the general formula (I) refers to a compound in which the nitrogen atom of the compound represented by the general formula (I) is quaternized by an R ⁰ group.
The R ⁰ group represents a C1-4 alkyl group or a C1-4 alkyl group substituted by a phenyl group.
The N-oxide of the compound represented by the general formula (I) refers to a compound obtained by oxidizing a nitrogen atom of the compound represented by the general formula (I).

[Method for producing compound of the present invention]
The compound of the present invention represented by the general formula (I) can be produced by the following methods or the methods described in Examples.

（式中、Ｒ^1-1、Ｒ^2-1、Ｒ^3-1、Ｒ^4-1、Ｒ^5-1は、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵と同じ意味を表わし、Ｎ¹は、窒素原子を表わす。ただし、いずれの窒素原子も四級アンモニウム塩またはＮ−オキシドを表わさないものとする。）
で示される化合物は、以下に示した方法によって製造することができる。 Among the compounds of the present invention represented by the general formula (I), compounds in which the nitrogen atom does not represent a quaternary ammonium salt or N-oxide, that is, a compound of the general formula (I-1)

(Wherein R ^1-1 , R ^2-1 , R ^3-1 , R ^4-1 and R ^5-1 represent the same meaning as R ¹ , R ² , R ³ , R ⁴ and R ⁵ ; N ¹ represents a nitrogen atom, provided that none of the nitrogen atoms represents a quaternary ammonium salt or N-oxide.
Can be produced by the method shown below.

（式中、Ｒ^1-1A、Ｒ^2-1A、Ｒ^3-1A、Ｒ^4-1A、Ｒ^5-1Aは、Ｒ^1-1、Ｒ^2-1、Ｒ^3-1、Ｒ^4-1、Ｒ^5-1と同じ意味を表わす。ただし、いずれもカルボキシル基、水酸基、アミノ基またはチオール基を含有する基を表わさないものとし、他の記号は前記と同じ意味を表わす。）
で示される化合物は、一般式（II）

（式中、Ｔは、Ｃ１〜４アルキル基、Ｃ５〜６の単環式炭素環、またはＣ５〜６の単環式炭素環または１〜２個の窒素原子および／または１個の酸素原子を含む５〜６員環の単環複素環によって置換されたＣ１〜４アルキル基を表わす。）
で示される化合物を、環化反応に付すことにより製造することができる。 Among the general formula (I-1), containing ^{R 1-1, R 2-1, R 3-1} , R 4-1, any carboxyl groups of R ^5-1 groups, hydroxyl group, an amino group or a thiol group A compound having no group represented by the general formula (I-1A)

^{(Wherein, R 1-1A, R 2-1A, R} 3-1A, R 4-1A, R 5-1A ^{is, R 1-1, R 2-1, R} 3-1, R 4-1, represent the same meanings as R ^5-1. However, any carboxyl group, a hydroxyl group, and shall not represent a group containing an amino group or a thiol group and the other symbols have the same meanings as described above.)
The compound represented by the general formula (II)

(Wherein, T represents a C1-4 alkyl group, a C5-6 monocyclic carbocycle, or a C5-6 monocyclic carbocycle or 1-2 nitrogen atoms and / or one oxygen atom. And represents a C1-4 alkyl group substituted by a 5- or 6-membered monocyclic heterocyclic ring.
Can be produced by subjecting the compound represented by to a cyclization reaction.

This cyclization method is known. For example, a tertiary amine (triethylamine, diisopropylethylamine, etc.), an acid (acetic acid, trifluoroacetic acid, etc.) or an acid (acetic acid, trifluoroacetic acid, etc.) is used in an organic solvent (dichloroethane, toluene, etc.). But by heating to 60-120 ° C. This reaction is a reaction that is cyclized simultaneously with cleavage of the T group.
This cyclization reaction can also be performed on a compound in which R ³ or R ⁴ represents a group containing a hydroxyl group.

This cyclization reaction can also be performed on compounds in which the nitrogen atom in the R ¹ , R ² , R ³ or R ⁴ group represents N-oxide.
If necessary, subsequent to this reaction, an operation for converting into a desired non-toxic salt may be performed by a known method.

（式中、Ｇ¹は、メチレン基またはビニレン基を表わし、Ｒ^1-1A-1は、

（基中、Ｒ^6-1Aは、Ｒ⁶と同じ意味を表わす。ただし、カルボキシル基、水酸基、アミノ基またはチオール基を含有する基を表わさないものとし、他の記号は前記と同じ意味を表わす。）を表わし、他の記号は前記と同じ意味を表わす。）
で示される化合物は、一般式（III）

（式中、すべての記号は、前記と同じ意味を表わす。）、
または一般式（IV）

で示される化合物と一般式（Ｖ）

で示される化合物を還元的アミノ化反応に付すことにより製造することができる。 In the general formula (I-1A), a compound in which G in R ^1-1A represents a methylene group or a vinylene group, that is, a compound represented by the general formula (I-1A-1)

(Wherein, G ¹ represents a methylene group or a vinylene group, and R ^1-1A-1 is

( ^Wherein , R ^6-1A has the same meaning as R ⁶ , provided that it does not represent a group containing a carboxyl group, a hydroxyl group, an amino group or a thiol group, and other symbols have the same meanings as described above. .), And the other symbols have the same meanings as described above. )
The compound represented by the general formula (III)

(In the formula, all symbols have the same meanings as described above.)
Or general formula (IV)

And a compound represented by the general formula (V)

Can be produced by subjecting a compound represented by the formula to a reductive amination reaction.

  This reductive amination reaction is known. For example, a reducing agent (sodium triacetoxyborohydride, sodium cyanoborohydride, etc.) in an organic solvent (for example, dichloroethane, dichloromethane, dimethylformamide, acetic acid and a mixture thereof) is used. ) In the presence of 0 to 40 ° C.

This reductive amination reaction can also be performed on a compound in which the nitrogen atom in the R ¹ group represents N-oxide.
The reductive amination reaction can also be performed on a compound in which R ³ or R ⁴ represents a group containing a hydroxyl group.

（すべての記号は、前記と同じ意味を表わす。）
で示される化合物は、一般式（VI）

（すべての記号は、前記と同じ意味を表わす。）
で示される化合物と一般式（Ｖ）で示される化合物を反応に付すことにより製造することができる。 In the general formula (I-1A), a compound in which G in R ^1-1A represents an ethylene group, that is, a compound represented by the general formula (I-1A-2)

(All symbols have the same meaning as described above.)
The compound represented by the general formula (VI)

(All symbols have the same meaning as described above.)
And a compound represented by the general formula (V).

  This reaction is known. For example, first, a PS-TsCl-HL resin (trade name, Argonaut Technologies, catalog) in an organic solvent (eg, dichloroethane, dichloromethane, etc.) in the presence of a tertiary amine (triethylamine, pyridine, etc.) No. 800366) and the compound represented by the general formula (VI) at a temperature of 0 to 40 ° C., and the obtained resin is reacted with a tertiary amine (diisopropyl) in an organic solvent (eg, acetonitrile, dichloroethane, dichloromethane, etc.). (E.g., ethylamine) at a temperature of 40 to 100 ° C with the compound represented by the general formula (V).

This reaction can also be carried out on compounds in which the nitrogen atom in the R ¹ , R ² , R ³ or R ⁴ group represents N-oxide.

（すべての記号は、前記と同じ意味を表わす。）
で示される化合物は、一般式（VII）

（式中、Ｘはハロゲン原子を表わし、他の記号は、前記と同じ意味を表わす。）
で示される化合物と一般式（Ｖ）で示される化合物を反応に付すことにより製造することができる。 In the general formula (I-1A), a compound in which G in R ^1-1A represents a single bond, that is, a compound represented by the general formula (I-1A-3)

(All symbols have the same meaning as described above.)
The compound represented by the general formula (VII)

(In the formula, X represents a halogen atom, and the other symbols have the same meanings as described above.)
And a compound represented by the general formula (V).

This reaction is known, and is carried out, for example, in an organic solvent (eg, dimethyl sulfoxide) in the presence of an alkali (potassium carbonate, sodium carbonate, etc.) at a temperature of 100 to 150 ° C.
This reaction can also be carried out on compounds in which the nitrogen atom in the R ¹ , R ² , R ³ or R ⁴ group represents N-oxide.

（すべての記号は、前記と同じ意味を表わす。）
で示される化合物は、一般式（XIII）

（すべての記号は、前記と同じ意味を表わす。）
で示される化合物と一般式（Ｖ）で示される化合物をアミド化反応に付すことにより製造することができる。 In the general formula (I-1A), a compound in which G in R ^1-1A represents —CO—, that is, a compound of the general formula (I-1A-5)

(All symbols have the same meaning as described above.)
The compound represented by the general formula (XIII)

(All symbols have the same meaning as described above.)
And the compound represented by the general formula (V) are subjected to an amidation reaction.

This amidation reaction is known, for example,
(1) a method using an acid halide,
(2) a method using a mixed acid anhydride,
And (3) a method using a condensing agent.

To illustrate these methods,
(1) A method using an acid halide is, for example, a method in which a carboxylic acid is reacted with an acid halide agent (oxalyl chloride, thionyl chloride, etc.) in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) or without a solvent. The reaction is carried out at 20 ° C. to reflux temperature, and the obtained acid halide is reacted with an amine in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) and an inert organic solvent (chloroform, methylene chloride, diethyl ether, In tetrahydrofuran) at 0 to 40 ° C. The reaction can also be carried out by reacting with an acid halide in an organic solvent (dioxane, tetrahydrofuran, etc.) using an aqueous alkali solution (aqueous sodium bicarbonate or sodium hydroxide solution) at a temperature of 0 to 40 ° C.

  (2) A method using a mixed acid anhydride is, for example, a method in which a carboxylic acid is dissolved in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, or the like) or without a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylamino). In the presence of pyridine or the like), react with an acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride, etc.) or an acid derivative (ethyl chloroformate, isobutyl chloroformate, etc.) at 0 to 40 ° C., and obtain the resulting mixture. The reaction is carried out by reacting an acid anhydride with an amine at 0 to 40 ° C in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.).

  (3) A method using a condensing agent includes, for example, a method in which a carboxylic acid and an amine are reacted with an tertiary amine (pyridine, triethylamine, In the presence or absence of dimethylaniline, dimethylaminopyridine, or the like, a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- [3- (dimethylamino) propyl] carbodiimide (EDC), , 1′-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodine, 1-propylphosphonic acid cyclic anhydride (PPA), etc., and 1-hydroxybenztriazole ( HOBt) with or without 0-40. In is carried out by reacting.

These reactions (1), (2) and (3) are desirably performed under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions.
This amidation reaction can also be performed on a compound in which R ³ or R ⁴ represents a group containing a hydroxyl group.
The amidation reaction can also be carried out on a compound in which the nitrogen atom in the R ¹ , R ² , R ³ or R ⁴ group is N-oxide.

（式中、Ｒ^1-1B、Ｒ^2-1B、Ｒ^3-1B、Ｒ^4-1B、Ｒ^5-1Bは、Ｒ^1-1、Ｒ^2-1、Ｒ^3-1、Ｒ^4-1、Ｒ^5-1と同じ意味を表わす。ただし、少なくとも１つの基がカルボキシル基、水酸基、アミノ基またはチオール基を含有する基を表わし、他の記号は前記と同じ意味を表わす。）
で示される化合物は、前記した方法によって製造した一般式（Ｉ−1A）のうち、Ｒ^1-1、Ｒ^2-1、Ｒ^3-1、Ｒ^4-1、Ｒ^5-1の少なくとも１つの基が保護基によって保護されたカルボキシル基、水酸基、アミノ基またはチオール基を含有する基を表わす化合物、すなわち、一般式（Ｉ−1A−４）

（式中、Ｒ^1-1A-4、Ｒ^2-1A-4、Ｒ^3-1A-4、Ｒ^4-1A-4、Ｒ^5-1A-4は、Ｒ^1-1、Ｒ^2-1、Ｒ^3-1、Ｒ^4-1、Ｒ^5-1と同じ意味を表わす。ただし、少なくとも１つの基が保護基によって保護されたカルボキシル基、水酸基、アミノ基またはチオール基を含有する基を表わし、他の記号は、前記と同じ意味を表わす。）
で示される化合物を保護基の脱保護反応に付すことにより製造することができる。 In the general formula (I-1), a compound in which at least one of R ¹ , R ² , R ³ , R ⁴ , and R ⁵ represents a group containing a carboxyl group, a hydroxyl group, an amino group, or a thiol group, , The general formula (I-1B)

( ^Wherein , R ^1-1B , R ^2-1B , R ^3-1B , R ^4-1B , R ^5-1B are R ^1-1 , R ^2-1 , R ^3-1 , R ^4-1 , It has the same meaning as R ^5-1 except that at least one group represents a group containing a carboxyl group, a hydroxyl group, an amino group or a thiol group, and the other symbols have the same meanings as described above.)
Is a compound represented by the formula (I-1A) produced by the method described above, wherein at least one of R ^1-1 , R ^2-1 , R ^3-1 , R ^4-1 and R ^5-1 is A compound in which the group represents a group containing a carboxyl group, a hydroxyl group, an amino group or a thiol group protected by a protecting group, that is, a compound represented by the general formula (I-1A-4)

^{(Wherein, R 1-1A-4, R 2-1A} -4, R 3-1A-4, R 4-1A-4, R 5-1A-4 is, R ^1-1, R ^2-1, R ^3-1 , R ^4-1 and R ^5-1 have the same meanings, provided that at least one group is a group containing a carboxyl, hydroxyl, amino or thiol group protected by a protecting group, Other symbols have the same meaning as described above.)
Can be produced by subjecting the compound represented by to a deprotection reaction of a protecting group.

Examples of the carboxyl-protecting group include a methyl group, an ethyl group, a t-butyl group, a benzyl group, and an allyl group.
Examples of the hydroxyl-protecting group include a methoxymethyl group, a 2-tetrahydropyranyl group, a t-butyldimethylsilyl group, a t-butyldiphenylsilyl group, an acetyl group, and a benzyl group.

Examples of the amino-protecting group include a benzyloxycarbonyl group, an allyloxycarbonyl group, a t-butoxycarbonyl group, a trifluoroacetyl group, and a 9-fluorenylmethoxycarbonyl group.
Examples of the thiol protecting group include a benzyl group, a methoxybenzyl group, an acetamidomethyl group, a triphenylmethyl group, and an acetyl group.

The protecting group for the carboxyl group, hydroxyl group, amino group or thiol group is not particularly limited as long as it is a group other than those described above that can be easily and selectively eliminated. For example, those described in TW Greene et al., Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience, New York, 1999 are used.
The deprotection reaction of the amino-protecting group is carried out by the method described above.

Deprotection reactions of carboxyl, hydroxyl or thiol protecting groups are well known and include, for example,
(1) alkaline hydrolysis,
(2) deprotection reaction under acidic conditions,
(3) deprotection reaction by hydrogenolysis,
(4) silyl group deprotection reaction,
(5) Deprotection reaction using a metal complex and the like.

To illustrate these methods,
(1) The deprotection reaction (for example, trifluoroacetyl group) by alkali hydrolysis is performed, for example, in an organic solvent (methanol, tetrahydrofuran, dioxane, etc.) in a hydroxide of an alkali metal (sodium hydroxide, potassium hydroxide, water). Lithium oxide), alkaline earth metal hydroxide (barium hydroxide, calcium hydroxide, etc.) or carbonate (sodium carbonate, potassium carbonate, etc.) or an aqueous solution thereof or a mixture thereof at 0 to 40 ° C. Done at temperature.

(2) The deprotection reaction under an acid condition (for example, a t-butoxycarbonyl group) is performed, for example, in an organic solvent (dichloromethane, chloroform, dioxane, ethyl acetate, anisole, etc.) in an organic acid (acetic acid, trifluoroacetic acid, Methanesulfonic acid or the like or an inorganic acid (hydrochloric acid, sulfuric acid or the like) or a mixture thereof (hydrogen bromide / acetic acid or the like) at a temperature of 0 to 100 ° C.

(3) The deprotection reaction by hydrogenolysis (for example, benzyl group, benzyloxycarbonyl group, allyloxycarbonyl group) includes, for example, a solvent (ether (tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, etc.), alcohol ( Methanol, ethanol, etc.), benzenes (benzene, toluene, etc.), ketones (acetone, methyl ethyl ketone, etc.), nitriles (acetonitrile, etc.), amides (dimethylformamide, etc.), water, ethyl acetate, acetic acid or two or more thereof In the presence of a catalyst (palladium-carbon, palladium black, palladium hydroxide, platinum oxide, Raney nickel, etc.) in a hydrogen atmosphere at normal pressure or under pressure or in the presence of ammonium formate at 0 to 200 ° C. Done at temperature.

(4) The deprotection reaction of the silyl group is performed, for example, in an organic solvent (tetrahydrofuran, acetonitrile, etc.) using tetrabutylammonium fluoride at a temperature of 0 to 40 ° C.

(5) The deprotection reaction using a metal complex is performed, for example, in an organic solvent (dichloromethane, dimethylformamide, tetrahydrofuran, etc.) in the presence of a trapping reagent (tributyltin hydride, dimedone, etc.) and / or an organic acid (acetic acid, etc.) The reaction is performed at a temperature of 0 to 40 ° C. using a metal complex (such as a tetrakistriphenylphosphine palladium (0) complex).

  As can be easily understood by those skilled in the art, the target compound of the present invention can be easily produced by properly using these deprotection reactions.

（式中、Ｒ^1-2、Ｒ^2-2、Ｒ^3-2、Ｒ^4-2、Ｒ^5-2は、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵と同じ意味を表わし、Ｎ²は、窒素原子を表わす。ただし、少なくとも１つの窒素原子が四級アンモニウム塩を表わすものとし、Ｑは、ハロゲン原子を表わすものとする。）
で示される化合物は、一般式（Ｉ−１）で示される化合物を一般式（XI）

（式中、Ｒ⁰は、Ｃ１〜４アルキル基またはフェニル基によって置換されたＣ１〜４アルキル基を表わし、Ｑは、ハロゲン原子を表わす。）
で示される化合物と反応させることにより製造することができる。 Compounds of the present invention represented by the general formula (I) in which at least one nitrogen atom represents a quaternary ammonium salt, that is, a compound represented by the general formula (I-2)

(Wherein R ^1-2 , R ^2-2 , R ^3-2 , R ^4-2 and R ^5-2 represent the same meaning as R ¹ , R ² , R ³ , R ⁴ and R ⁵ ; N ² represents a nitrogen atom, provided that at least one nitrogen atom represents a quaternary ammonium salt, and Q represents a halogen atom.
Is a compound represented by the general formula (I-1)

(In the formula, R ⁰ represents a C 1-4 alkyl group or a C 1-4 alkyl group substituted by a phenyl group, and Q represents a halogen atom.)
The compound can be produced by reacting with the compound represented by

  This reaction is known, and is carried out, for example, in an organic solvent (acetone, dimethylformamide, methyl ethyl ketone, etc.) at a temperature of 0 to 40 ° C.

（式中、Ｒ^1-3、Ｒ^2-3、Ｒ^3-3、Ｒ^4-3、Ｒ^5-3は、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵と同じ意味を表わし、Ｎ³は、窒素原子を表わす。ただし、少なくとも１つの窒素原子がＮ−オキシドを表わすものとする。）
で示される化合物は、一般式（Ｉ−１）で示される化合物を酸化反応に付すことにより製造することができる。 Compounds of the present invention represented by the general formula (I) in which at least one nitrogen atom represents an N-oxide, that is, a compound represented by the general formula (I-3)

(Wherein, R ^1-3 , R ^2-3 , R ^3-3 , R ^4-3 , and R ^5-3 represent the same meaning as R ¹ , R ² , R ³ , R ⁴ , and R ⁵ ; N ³ represents a nitrogen atom, provided that at least one nitrogen atom represents an N-oxide.
Can be produced by subjecting a compound represented by the general formula (I-1) to an oxidation reaction.

  This oxidation reaction is known. For example, in an appropriate organic solvent (dichloromethane, chloroform, benzene, hexane, t-butyl alcohol, etc.), an excess of an oxidizing agent (hydrogen peroxide, sodium periodate, acyl nitrite, In the presence of sodium perborate, peracids (eg, 3-chloroperbenzoic acid, peracetic acid, etc.), oxone (trade name of potassium peroxymonosulfate), potassium permanganate, chromic acid, etc. The reaction is performed at a temperature of 60 ° C.

  The compound represented by the general formula (II) can be produced by the following reaction scheme 1.

  In the above reaction schemes, each reaction is carried out by a known method. In the above reaction scheme, the compounds represented by the general formulas (IX), (X), (XI) and (XII) used as starting materials are known per se or are known per se. It can be easily manufactured by the method described above.

In each of the reactions herein, the reaction product is purified by conventional purification means, for example, distillation under normal pressure or reduced pressure, high-performance liquid chromatography using silica gel or magnesium silicate, thin-layer chromatography, or column chromatography. Alternatively, it can be purified by a method such as washing and recrystallization. Purification may be performed for each reaction, or may be performed after several reactions are completed.
Other starting materials and each reagent in the present invention are known per se or can be produced by a known method.

[Pharmacological activity]
The effectiveness of the compound of the present invention represented by the general formula (I) was proved by, for example, the following experiment.

  As described above, in order to screen for a compound that inhibits the binding of HIV to CXCR4 or CCR5, which is a receptor on CD4-positive cells, it is more straightforward to use an HIV virus-based assay system. It is an effective method. However, the use of HIV virus for large-scale screening is not practical because of its difficulty in handling. On the other hand, since both macrophage-tropic (R5) HIV-1 and RANTES, MIP-1α and MIP-1β bind to CCR5, CCR5 binding sites on both the HIV side and RANTES, MIP-1α and MIP-1β sides, and It can be expected that the RANTES, MIP-1α, MIP-1β and HIV binding sites on the CCR5 side have some common characteristics. Therefore, to find a compound that inhibits the adsorption of HIV virus to cells, which has a different mechanism of action from existing anti-AIDS drugs (reverse transcription inhibitors and protease inhibitors), it is an endogenous ligand for CCR5 instead of HIV. Assay systems using RANTES, MIP-1α, and MIP-1β are available.

  Specifically, as a system for screening for a compound that inhibits the binding between RANTES and CCR5, for example, since CCR5 is a G protein-coupled seven-transmembrane receptor, RANTES induces calcium (Ca ) A system for measuring the effect of ions on the transient rise is feasible. A similar idea is possible because both T cell-tropic (X4) HIV and SDF-1 bind to CXCR4.

[experimental method]
(1) Isolation of human CCR5 gene Human placenta cDNA was prepared using Marathon cDNA amplification kit (Clontech). The PCR primers hCCR5XbaI-F1: 5'-AGCTAGTCTAGATCCGTTCCCTACAAGAAACTCTCC-3 '(SEQ ID NO: 1) and hCCR5XbaI-R1: 5'-AGCTAGTCTAGAGTGCACAACTCTGACTGGTCACCCA-3' (SEQ ID NO: 2) are based on GenBank 549.
A PCR reaction (95 ° C. for 2 minutes → [95 ° C. for 30 seconds, 60 ° C. for 45 seconds, 72 ° C. for 1 minute] × 35 times) using human placenta cDNA as a template and Ex Taq (Takara) was performed. Was. The amplified PCR product was subjected to 1% agarose gel electrophoresis, purified using a QIAquick Gel Extraction Kit (QIAGEN), and cut with a restriction enzyme XbaI. The cut fragment was ligated to the expression vector pEF-BOS-bsr using DNA Ligation Kit Ver. 2 (Takara) and transformed into Escherichia coli DH5a. This plasmid pEF-BOS-bsr / hCCR5 was prepared and its DNA sequence was confirmed.

(2) Culture of CHO cells
CHO-dhfr (-) was cultured using Ham's F-12 (containing fetal bovine serum (10%), penicillin (50 U / ml), and streptomycin (50 mg / ml)). The transduced cells were cultured by adding blasticidin (5 mg / ml) as described above.

(3) Transduction of CHO cells
CHO-dhfr (-) cells were transduced with the plasmid pEF-BOS-bsr / hCCR5 using DMRIE-C reagent (Gibco BRL). Forty-eight hours later, the medium was replaced with a medium containing 5 mg / ml blasticidin for selection, and stable overexpressed cells were established.

Ｅｃ：ＲＡＮＴＥＳによるＣａ²⁺一過性上昇の測定値
Ｅａ：試験化合物を添加した時のＲＡＮＴＥＳによるＣａ²⁺一過性上昇の測定値 (4) Inhibition experiment on binding between RANTES and CCR5 (activity of RANTES to induce transient increase in Ca ion) Established human CCR5 stably overexpressing CHO cells (CCR5 / CHO cells) were transformed into Ham's F-12 medium and FBS (10% ) And wound into a 96-well plate at 3.0 × 10 ⁶ cells / well. After culturing at 37 ° C. for 1 day, the culture supernatant was removed, and 80 μl / well of Ham's F-12 medium (containing Fura-2AM (5 μM), Probenecid (2.5 mM) and HEPES (20 mM; pH 7.4)). Was added and incubated at 37 ° C. for 1 hour in the dark. After washing twice with a 1 × Hanks / HEPES (20 mM; pH 7.4) solution, the same solution was added at 100 μl / well. After 3 minutes from the addition of the test compound, the recombinant human RANTES (PeproTech) diluted with 1 × Hanks / HEPES (20 mM; pH 7.4) was added to the CCR5 / CHO cells incorporating the Fura-2AM. A concentration of 10 nM was added. The transient increase in intracellular Ca ²⁺ concentration induced by human RANTES was measured using a 96-well Ca ²⁺ detector (Hamamatsu Photonics), and the inhibition rate (%) of the test compound was calculated by the following formula. Was calculated by

Ec: Measured value of Ca ²⁺ transient increase by RANTES Ea: Measured value of Ca ²⁺ transient increase by RANTES when test compound was added

As a result, the compound of the present invention showed 50% or more inhibition at 10 μM. For example, the compound of Example 2 had an IC ₅₀ value of 0.027 μM, and the compound of Example 3 had an IC ₅₀ value of 0.37 μM.
Although a system for finding a compound having an adsorption inhibitory effect on a CCR5-directed HIV strain has been described above, it is of course possible to find a compound that inhibits the action of CCR5 or its ligand using this system. Similarly, it is possible to find compounds that inhibit the action of other chemokine receptors and their ligands. For example, a system for finding a compound that inhibits the action of CCR2 or its ligand can be constructed. Like CCR5, CCR2 is a G protein-coupled seven-transmembrane receptor. Therefore, by measuring the effect of its ligand, for example, MCP-1 on the transient rise of Ca ions induced through CCR2, It is feasible.

Ｅｃ：ＭＣＰ−１によるＣａ²⁺一過性上昇の測定値
Ｅａ：試験化合物を添加した時のＭＣＰ−１によるＣａ²⁺一過性上昇の測定値 (5) Inhibition experiment on the binding between MCP-1 and CCR2 (activity of MCP-1 to induce a transient increase in Ca ions) Cells expressing human CCR2, for example, human monocyte cell line THP-1 (ATCC No. TIB) -202) was suspended in RPMI1640 medium containing FBS (10%), Fura2-AM (5 μM), probenecid (Probenecid, 2.5 mM) and HEPES (20 mM, pH 7.4) at 5.0 × 10 ⁶ cells / ml. The solution was kept at 37 ° C. for 30 minutes in a turbid and light-shielded state. 4 to 8 times 1 × Hanks / HEPES (20 mM, pH 7.4) / Probenecid (2.5 mM) was added, and the mixture was further kept at 37 ° C. for 30 minutes in a light-shielded state. After washing the cells with a 1 × Hanks / HEPES (20 mM, pH 7.4) / Probenecid (2.5 mM) solution, the cells were resuspended at 2.0 × 10 ⁶ cells / ml with the same solution, and 100 μl was added to a 96-well plate. Three minutes after the addition of the test compound solution, recombinant human MCP-1 (PeproTech) diluted with 1 × Hanks / HEPES (20 mM, pH 7.4) / Probenecid (2.5 mM) was added at a final concentration of 30 nM. The transient increase in intracellular Ca ²⁺ concentration induced by human MCP-1 was measured using a 96-well Ca ²⁺ detector (Hamamatsu Photonics), and the inhibition rate (%) of the test compound was calculated as follows: It was calculated by the equation.

Ec: Measured value of Ca ²⁺ transient increase by MCP-1 Ea: Measured value of Ca ²⁺ transient increase by MCP-1 when a test compound was added

[toxicity]
The toxicity of the compound of the present invention is extremely low, and it can be determined that the compound is sufficiently safe for use as a medicament.

[Application to pharmaceutical products]
In animals including humans, in particular, humans, the compound of the present invention represented by the general formula (I) controls the action of chemokines / chemokine receptors, so that various inflammatory diseases, asthma, atopic dermatitis, urticaria, Allergic diseases (allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteropathy, etc.), nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, suppression of ischemia-reperfusion injury, multiple occurrence Treatment of sclerosis, ulcerative colitis, acute respiratory distress syndrome, shock due to bacterial infection, diabetes, autoimmune disease, transplant rejection, immunosuppression, prevention of cancer metastasis, prevention and / or treatment of acquired immunodeficiency syndrome Useful for

  In order to use the compound of the present invention represented by the general formula (I), a non-toxic salt thereof, an acid addition salt thereof, or a hydrate thereof for the above-mentioned purpose, it is usually necessary to use systemically or topically orally or parenterally. It is administered in the form.

  The dosage varies depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., and is usually orally administered once to several times a day, in the range of 1 mg to 1000 mg per adult per administration. Or parenterally (preferably intravenously) once to several times daily, in the range of 1 mg to 100 mg per adult, or 1 hour to 24 hours daily. It is continuously administered intravenously in a range.

Of course, as described above, since the dose varies depending on various conditions, a dose smaller than the above-mentioned dose may be sufficient, or may be required beyond the range.
When the compound of the present invention is administered, it is used as a solid preparation for oral administration, a liquid preparation for oral administration, and an injection, parenteral preparation, suppository and the like for parenteral administration.
Solid preparations for internal use for oral administration include tablets, pills, capsules, powders, granules and the like. Capsules include hard capsules and soft capsules.

  In such solid dosage forms for internal use, the one or more active substances can be as such or excipients (lactose, mannitol, glucose, microcrystalline cellulose, starch, etc.), binders (hydroxypropylcellulose, polyvinylpyrrolidone, It is mixed with a disintegrator (such as calcium glycolate), a lubricant (such as magnesium stearate), a stabilizer, a solubilizer (such as glutamic acid and aspartic acid), and the like. It is used after being formulated. If necessary, it may be coated with a coating agent (sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, etc.), or may be coated with two or more layers. Also included are capsules of absorbable materials such as gelatin.

  Liquid preparations for oral administration include pharmaceutically acceptable solutions, suspensions, emulsions, syrups, elixirs and the like. In such a solution, one or more active substances are dissolved, suspended or emulsified in a commonly used diluent (such as purified water, ethanol or a mixture thereof). Further, the liquid preparation may contain a wetting agent, a suspending agent, an emulsifier, a sweetening agent, a flavoring agent, a fragrance, a preservative, a buffer and the like.

  Injections for parenteral administration include solutions, suspensions, emulsions, and solid injections which are dissolved or suspended in a solvent before use. Injectables are used by dissolving, suspending or emulsifying one or more active substances in a solvent. As the solvent, for example, distilled water for injection, physiological saline, vegetable oil, propylene glycol, polyethylene glycol, alcohols such as ethanol and the like, and a combination thereof are used. Further, this injection may contain a stabilizer, a solubilizing agent (glutamic acid, aspartic acid, polysorbate 80 (registered trademark), etc.), a suspending agent, an emulsifier, a soothing agent, a buffer, a preservative, and the like. . These are manufactured and prepared by sterilization or aseptic operation in the final step. In addition, a sterile solid preparation, for example, a lyophilized product, can be manufactured and dissolved in aseptic or sterile distilled water for injection or other solvents before use.

  Other formulations for parenteral administration include those containing one or more active substances and are formulated according to conventional methods for external use, ointments, salves, inhalants, sprays, suppositories and vaginal administration. Pessaries etc. are included.

  Sprays may contain, in addition to the commonly used diluents, buffers such as sodium bisulfite, which provide isotonicity with stabilizers, e.g., isotonic agents such as sodium chloride, sodium citrate, or citric acid. It may be. Methods for producing sprays are described in detail, for example, in US Pat. Nos. 2,868,691 and 3,095,355.

  The compound of the present invention represented by the general formula (I), a quaternary ammonium salt thereof, an N-oxide thereof or a non-toxic salt thereof may be used for other drugs such as a prophylactic and / or therapeutic agent for HIV infection ( In particular, a prophylactic and / or therapeutic agent for AIDS) may be used. In this case, these drugs may be separately or simultaneously mixed and formulated with pharmacologically acceptable excipients, binders, disintegrants, lubricants, stabilizers, solubilizing agents, diluents and the like. , Or orally or parenterally as a pharmaceutical composition for the prevention and / or treatment of HIV infection.

  The compound represented by the general formula (I) of the present invention, a quaternary ammonium salt thereof, an N-oxide thereof or a non-toxic salt thereof may be used as a prophylactic and / or therapeutic agent for other HIV infections (in particular, AIDS HIV-1 which has acquired resistance to prophylactic and / or therapeutic agents). Therefore, it can be used for HIV-infected patients in which other preventive and / or therapeutic agents for HIV infection have become ineffective. In this case, the compound of the present invention may be used alone, or may be used in combination with a preventive and / or therapeutic agent for HIV infection in which the infected HIV-1 strain has acquired resistance or other agents. good.

  The present invention combines the compounds of general formula (I), their quaternary ammonium salts, their N-oxides or their non-toxic salts with drugs that do not inhibit HIV infection, and are more effective than HIV alone in treating HIV infection. Also includes those with an enhanced preventive and / or therapeutic effect.

  Examples of other prophylactic and / or therapeutic agents for HIV infection used in combination with the compounds of the present invention represented by the general formula (I), their quaternary ammonium salts, their N-oxides or their non-toxic salts Examples thereof include reverse transcriptase inhibitors, protease inhibitors, chemokine antagonists (eg, CCR2 antagonists, CCR3 antagonists, CCR4 antagonists, CCR5 antagonists, CXCR4 antagonists, etc.), fusion inhibitors, HIV-1 surfaces Antibodies to antigens, HIV-1 vaccines and the like can be mentioned.

  Specific examples of the reverse transcriptase inhibitor include (1) the nucleic acid-based reverse transcriptase inhibitors zidovudine (trade name: retrovir), didanosine (trade name: Videx), zalcitabine (trade name: hybrid), stavudine ( (2) Non-products (trade name: Zelit), lamivudine (trade name: epivir), abacavir (trade name: Ziagen), adefovir, adefovir dipivoxil, entry cytabine (trade name: coviracil), PMPA (trade name: tenofovir) Examples include the nucleic acid reverse transcriptase inhibitors nevirapine (trade name: Vilamune), delavirdine (trade name: rescripter), efavirenz (trade names: Sastiva, Stocklin), capravirin (AG1549), and the like.

  Specific examples of protease inhibitors include indinavir (trade name: Crixiban), ritonavir (trade name: Novia), nelfinavir (trade name: viracept), saquinavir (trade names: Invirase, Fort Base), and amprinavir (trade name) Name: ezinelaser), lopinavir (trade name: Kaletra), tipranavir and the like.

Chemokine antagonists include endogenous ligands of the chemokine receptor, or derivatives thereof and non-peptidic low molecular weight compounds, or antibodies to the chemokine receptor.
Specific examples of endogenous ligands for chemokine receptors include MIP-1α, MIP-1β, RANTES, SDF-1α, SDF-1β, MCP-1, MCP-2, MCP-4, eotaxin, MDC and the like.
Specific examples of the derivative of the endogenous ligand include AOP-RANTES, Met-SDF-1α, and Met-SDF-1β.
Specific examples of the chemokine receptor antibody include Pro-140.

As the CCR2 antagonist, specifically, WO99 / 07351, WO99 / 40913, WO00 / 46195, WO00 / 46196, WO00 / 46197, WO00 / 46198, WO00 / 46199, WO00 / 69432 And WO00 / 69815 or Bioorg. Med. Chem. Lett., 10 , 1803 (2000).

  As the CCR3 antagonist, specifically, DE19837386, WO99 / 55324, WO99 / 55330, WO00 / 04003, WO00 / 27800, WO00 / 27835, WO00 / 27843, WO00 / 29377, WO00 / 31032, WO00 / 31033, WO00 / 34278, WO00 / 35449, WO00 / 35451, WO00 / 35452, WO00 / 35453, WO00 / 35454, WO00 / 35876, WO00 / 35877, WO00 / 41685, WO00 / 51607, WO00 / 51608, WO00 / 51609, WO00 / 51610, WO00 / 53172, WO00 / 53600, WO00 / 58305, WO00 / 59497, WO00 / 59498, WO00 / 59502, WO00 / 59503, WO00 / 62814, WO00 / 73327, or WO01 / 09088.

As the CCR5 antagonist, specifically, WO99 / 17773, WO99 / 32100, WO00 / 06085, WO00 / 06146, WO00 / 10965, WO00 / 06153, WO00 / 21916, WO00 / 37455 EP1013276, WO00 / 38680, WO00 / 39125, WO00 / 40239, WO00 / 42045, WO00 / 53175, WO00 / 42852, WO00 / 66551, WO00 / 66558, WO00 / 66559, WO00 / 66141, WO00 / 68203, JP2000309598, WO00 / 51607, WO00 / 51608, WO00 / 51609, WO00 / 51610, WO00 / 56729, WO00 / 59497, WO00 / 59498, WO00 / 59502 No. WO00 / 59503, WO00 / 76933, WO98 / 25605, WO99 / 04794, WO99 / 38514 or the compounds described in Bioorg.Med.Chem.Lett., 10 , 1803 (2000). Can be

Specific examples of the CXCR4 antagonist include AMD-3100, T-22, KRH-1120, and the compounds described in WO00 / 66112.
Specific examples of the fusion inhibitor include T-20 (pentafuside), T-1249 and the like.

  The above concomitant drugs are examples, and the present invention is not limited to these.

Typical clinical dosages of typical reverse transcriptase inhibitors and protease inhibitors are, for example, as shown below, but the present invention is not limited thereto.
Zidovudine: 100 mg capsule, 200 mg at a time, 3 times a day;
300 mg tablet, 300 mg at a time, twice a day;
Didanosine: 25-200 mg tablet, 125-200 mg at a time, twice daily;
Zalcitabine: 0.375 mg to 0.75 mg tablet, 0.75 mg at a time, 3 times a day;
Stavudine: 15-40 mg capsules, 30-40 mg at a time, twice daily;
Lamivudine: 150 mg tablet, 150 mg at a time, twice a day;
Abacavir: 300 mg tablet, 300 mg at a time, twice a day;
Nevirapine: 200 mg tablet, 200 mg at a time, once a day for 14 days, then twice a day;
Delavirdine: 100 mg tablet, 400 mg at a time, 3 times a day;
Efavirenz: 50-200 mg capsule, 600 mg at a time, once a day;
Indinavir: 200-400 capsules, 800 mg at a time, three times a day;
Ritonavir: 100 mg capsule, 600 mg at a time, twice daily;
Nelfinavir: 250 mg tablet, 750 mg at a time, 3 times a day;
Saquinavir: 200 mg capsule, 1, 200 mg at a time, 3 times a day;
Amprenavir: 50-150 mg tablet, 1, 200 mg at a time, twice a day.

Hereinafter, the present invention will be described in detail by reference examples and examples, but the present invention is not limited to these.
The solvent in the parenthesis shown in the chromatographic separation and in the TLC indicates the elution solvent or developing solvent used, and the ratio indicates the volume ratio.
The solvent in parentheses shown in the NMR section indicates the solvent used for the measurement.

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸（10.5ｇ）のメタノール（３４０ｍｌ）溶液に、ｎ−ブチルアミン（4.2ｍｌ）、Ｎ−ベンジル−４−ピペリドン（7.9ｍｌ）、ベンジルイソニトリル（5.2ｍｌ）を加えた。反応混合物を５５℃で一晩撹拌した。反応混合物を濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム：メタノール＝１００：１→７５：１→５０：１）によって精製し、以下の物性値を有する標題化合物（19.8ｇ）を得た。
ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.38-7.15 (m, 10H), 4.58 (d, J = 9.6 Hz, 1H), 4.39 (d, J = 15.0 Hz, 1H), 4.23 (d, J = 15.0 Hz, 1H), 3.70-3.30 (m, 3H), 3.50 (s, 2H), 2.79-2.30 (m, 6H), 2.08-1.88 (m, 2H), 1.88-1.70 (m, 3H), 1.50-1.28 (m, 2H), 1.38 (s, 9H), 0.98 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.91 (d, J = 6.6 Hz, 3H)。 Reference Example 1
(2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methyl-N-butyl-N- [4-benzylaminocarbonyl-1-benzylpiperidin-4-yl] pentanamide

In a solution of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid (10.5 g) in methanol (340 ml), n-butylamine (4.2 ml) and N-benzyl-4 were added. -Piperidone (7.9 ml), benzylisonitrile (5.2 ml) were added. The reaction mixture was stirred at 55 C overnight. The reaction mixture was concentrated. The obtained residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1 → 75: 1 → 50: 1) to give the title compound (19.8 g) having the following physical data.
TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.38-7.15 (m, 10H), 4.58 (d, J = 9.6 Hz, 1H), 4.39 (d, J = 15.0 Hz, 1H), 4.23 (d, J = 15.0 Hz) , 1H), 3.70-3.30 (m, 3H), 3.50 (s, 2H), 2.79-2.30 (m, 6H), 2.08-1.88 (m, 2H), 1.88-1.70 (m, 3H), 1.50-1.28 (m, 2H), 1.38 (s, 9H), 0.98 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.91 (d, J = 6.6 Hz, 3H).

参考例１で製造した化合物（19.8ｇ）のジクロロメタン（６５ｍｌ）溶液に、氷冷下で、トリフルオロ酢酸（５０ｍｌ）を加えた。反応混合物を室温で１時間撹拌した。反応混合物に、ジクロロメタンを加え、炭酸ナトリウム水溶液で中和し、抽出した。抽出物を水、飽和塩化ナトリウム水溶液で洗浄し、無水硫酸ナトリウムで乾燥し、濃縮し、以下の物性値を有する標題化合物を得た。得られた残渣をさらに精製することなしに、次の反応に用いた。
ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）。 Reference Example 2
(2R, 3R) -2-Amino-3-hydroxy-4-methyl-N-butyl-N- [4-benzylaminocarbonyl-1-benzylpiperidin-4-yl] pentanamide

To a solution of the compound (19.8 g) produced in Reference Example 1 in dichloromethane (65 ml) was added trifluoroacetic acid (50 ml) under ice-cooling. The reaction mixture was stirred at room temperature for 1 hour. Dichloromethane was added to the reaction mixture, neutralized with an aqueous solution of sodium carbonate, and extracted. The extract was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give the title compound having the following physical data. The obtained residue was used for the next reaction without further purification.
TLC: Rf 0.38 (chloroform: methanol = 10: 1).

参考例２で製造した化合物のトルエン（２００ｍｌ）溶液に、酢酸（１５ｍｌ）を加えた。反応混合物を８０℃で、４５分間撹拌した。反応混合物を酢酸エチルで希釈し、炭酸ナトリウム水溶液で中和し、抽出した。抽出物を飽和塩化ナトリウム水溶液で洗浄し、無水硫酸ナトリウムで乾燥し、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル：メタノール＝２５：１）によって精製し、以下の物性値を有する本発明化合物（12.9ｇ）を得た。
ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.36-7.22 (m, 5H), 4.10 (d, J = 2.7 Hz, 1H), 3.60 (s, 2H), 3.47 (m, 1H), 3.38-3.25 (m, 2H), 2.96 (m, 1H), 2.87-2.73 (m, 3H), 2.25-1.94 (m, 4H), 1.82 (m, 1H), 1.64 (m, 1H), 1.53-1.27 (m, 3H), 0.96 (d, J = 6.6 Hz, 6H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 1
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9-benzyl-1,4,9-triazaspiro [5.5] undecane

Acetic acid (15 ml) was added to a toluene (200 ml) solution of the compound produced in Reference Example 2. The reaction mixture was stirred at 80 ° C. for 45 minutes. The reaction mixture was diluted with ethyl acetate, neutralized with aqueous sodium carbonate and extracted. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate: methanol = 25: 1) to give the compound of the present invention (12.9 g) having the following physical data.
TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.36-7.22 (m, 5H), 4.10 (d, J = 2.7 Hz, 1H), 3.60 (s, 2H), 3.47 (m, 1H), 3.38-3.25 (m, 2H), 2.96 (m, 1H), 2.87-2.73 (m, 3H), 2.25-1.94 (m, 4H), 1.82 (m, 1H), 1.64 (m, 1H), 1.53-1.27 (m, 3H) , 0.96 (d, J = 6.6 Hz, 6H), 0.95 (t, J = 7.5 Hz, 3H).

実施例１で製造した化合物（12.67ｇ）のメタノール（１６０ｍｌ）溶液に、アルゴンガス雰囲気下、２０％水酸化パラジウム炭素（1.3ｇ）を加えた。反応混合物を水素ガス雰囲気下、室温で、１２時間撹拌した。反応混合物をセライト（商品名）を用いて、ろ過し、ろ液を濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム：ヘキサン＝３：１→クロロホルム：メタノール＝１００：１→５０：１→３０：１→２０：１→１０：１）によって精製した。得られた化合物に４Ｎ塩化水素酢酸エチル溶液（１０ｍｌ）を加え、濃縮し、以下の物性値を有する本発明化合物（8.6ｇ）を得た。
ＴＬＣ：Ｒｆ 0.16（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ 4.15 (d, J=2.1Hz, 1H), 3.95 (m, 1H), 3.71 (m, 1H), 3.52 (m, 1H), 3.42-3.31 (m, 2H), 3.21 (m, 1H), 3.21 (dd, J=9.6, 2.1Hz, 1H), 2.48-2.32 (m, 2H), 2.23 (m, 1H), 2.14-1.96 (m, 2H), 1.72 (m, 1H), 1.55-1.33 (m, 3H), 1.02-0.92 (m, 9H)；
比旋光度：［α］_D +13.9 （c 1.00、メタノール、28℃）。 Reference Example 3
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

To a solution of the compound prepared in Example 1 (12.67 g) in methanol (160 ml) was added 20% palladium hydroxide carbon (1.3 g) under an argon gas atmosphere. The reaction mixture was stirred at room temperature under a hydrogen gas atmosphere for 12 hours. The reaction mixture was filtered using Celite (trade name), and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (chloroform: hexane = 3: 1 → chloroform: methanol = 100: 1 → 50: 1 → 30: 1 → 20: 1 → 10: 1). To the obtained compound was added a 4N solution of hydrogen chloride in ethyl acetate (10 ml), and the mixture was concentrated to give the compound of the present invention (8.6 g) having the following physical data.
TLC: Rf 0.16 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 4.15 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.71 (m, 1H), 3.52 (m, 1H), 3.42-3.31 (m, 2H), 3.21 (m, 1H), 3.21 (dd, J = 9.6, 2.1Hz, 1H), 2.48-2.32 (m, 2H), 2.23 (m, 1H), 2.14-1.96 (m, 2H), 1.72 (m, 1H), 1.55-1.33 (m, 3H), 1.02-0.92 (m, 9H);
Specific rotation: [α] _D +13.9 (c 1.00, methanol, 28 ° C.).

Reference Examples 3 (1) to 3 (9)
Using the corresponding amino acid derivative instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid and the corresponding amine derivative instead of n-butylamine, The same operation as in Reference Example 1 → Reference Example 2 → Example 1 → Reference Example 3 was carried out to obtain the compounds shown below.

ＴＬＣ：Ｒｆ 0.18（クロロホルム：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ4.02 (dd, J = 7.8, 4.6 Hz, 1H), 3.82-3.70 (m, 2H), 3.39 (m, 4H), 2.34-2.09 (m, 4H), 1.88-1.50 (m, 5H), 1.37 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.94 (d, J = 6.5 Hz, 3H)；
比旋光度：［α］_D -38.8 （c 1.04、メタノール、23℃）。 Reference example 3 (1)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.18 (chloroform: methanol = 4: 1);
NMR (CD ₃ OD): δ 4.02 (dd, J = 7.8, 4.6 Hz, 1H), 3.82-3.70 (m, 2H), 3.39 (m, 4H), 2.34-2.09 (m, 4H), 1.88- 1.50 (m, 5H), 1.37 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.94 (d, J = 6.5 Hz, 3H);
Specific rotation: [α] _D -38.8 (c 1.04, methanol, 23 ° C).

ＴＬＣ：Ｒｆ 0.08（クロロホルム：メタノール：酢酸＝９０：１０：１）；
ＮＭＲ（CD₃OD）：δ4.05 (dd, J = 7.8, 4.8 Hz, 1H), 3.84-3.68 (m, 2H), 3.46-3.34 (m, 4H), 2.40-2.04 (m, 4H), 1.83-1.46 (m, 10H), 1.39 (sextet, J = 7.5 Hz, 2H),
1.05-0.86 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)；
比旋光度：［α］_D -37.5 （c 1.04、メタノール、18℃）。 Reference example 3 (2)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.08 (chloroform: methanol: acetic acid = 90: 10: 1);
NMR (CD ₃ OD): δ 4.05 (dd, J = 7.8, 4.8 Hz, 1H), 3.84-3.68 (m, 2H), 3.46-3.34 (m, 4H), 2.40-2.04 (m, 4H), 1.83-1.46 (m, 10H), 1.39 (sextet, J = 7.5 Hz, 2H),
1.05-0.86 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H);
Specific rotation: [α] _D -37.5 (c 1.04, methanol, 18 ° C).

ＴＬＣ：Ｒｆ 0.32（ブタノール：酢酸：水＝４：２：１）；
ＮＭＲ（CD₃OD）：δ4.16 (d, J = 2.0 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.52 (m, 1H), 3.37 (m, 1H), 3.28 (m, 1H), 3.22-3.13 (m, 2H), 2.46-1.93 (m, 6H), 1.80-1.64 (m, 5H), 1.48-1.15 (m, 6H), 1.02-0.87 (m, 5H)；
比旋光度：［α］_D +1.22 （c 1.04、メタノール、26℃）。 Reference example 3 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.32 (butanol: acetic acid: water = 4: 2: 1);
NMR (CD ₃ OD): δ 4.16 (d, J = 2.0 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.52 (m, 1H), 3.37 (m, 1H), 3.28 (m, 1H), 3.22-3.13 (m, 2H), 2.46-1.93 (m, 6H), 1.80-1.64 (m, 5H), 1.48-1.15 (m, 6H), 1.02-0.87 (m, 5H) ;
Specific rotation: [α] _D +1.22 (c 1.04, methanol, 26 ° C.).

ＴＬＣ：Ｒｆ 0.05（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.13 (d, J = 2.0 Hz, 1H), 4.01-3.91 (m, 3H), 3.70 (m, 1H), 3.59-3.32 (m, 6H), 3.20 (m, 1H), 2.47-2.19 (m, 3H), 2.11-1.69 (m, 5H), 1.47-1.17 (m, 5H), 0.70 (t, J = 7.0 Hz, 3H)。 Reference example 3 (4)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.05 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.13 (d, J = 2.0 Hz, 1H), 4.01-3.91 (m, 3H), 3.70 (m, 1H), 3.59-3.32 (m, 6H), 3.20 (m, 1H), 2.47-2.19 (m, 3H), 2.11-1.69 (m, 5H), 1.47-1.17 (m, 5H), 0.70 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.04（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.00 (d, J = 2.0 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.53 (m, 1H), 3.40-3.34 (m, 3H), 3.21 (m, 1H), 2.46-2.19 (m, 4H), 2.08 (m, 1H), 1.92-1.83 (m, 2H), 1.70-1.50 (m, 6H), 1.45-1.26 (m, 5H), 0.97 (t, J = 7.0 Hz, 3H)。 Reference example 3 (5)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.04 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.00 (d, J = 2.0 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.53 (m, 1H), 3.40-3.34 (m, 3H) , 3.21 (m, 1H), 2.46-2.19 (m, 4H), 2.08 (m, 1H), 1.92-1.83 (m, 2H), 1.70-1.50 (m, 6H), 1.45-1.26 (m, 5H) , 0.97 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.15（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ4.15 (d, J = 2.1 Hz, 1H), 3.96 (m, 1H), 3.71 (m, 1H), 3.56-3.25 (m, 3H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 3.13 (m, 1H), 2.51-1.95 (m, 5H), 1.75 (m, 1H), 1.49 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Reference example 3 (6)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.15 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 4.15 (d, J = 2.1 Hz, 1H), 3.96 (m, 1H), 3.71 (m, 1H), 3.56-3.25 (m, 3H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 3.13 (m, 1H), 2.51-1.95 (m, 5H), 1.75 (m, 1H), 1.49 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.16（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ4.16 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.47 (m, 1H), 3.41-3.24 (m, 4H), 3.12 (m, 1H), 2.44 (m, 1H), 2.33 (m, 1H), 2.19 (m, 1H), 2.08 (m, 1H), 2.03-1.89 (m, 2H), 1.84-1.62 (m, 4H), 1.50 (m, 1H), 1.40-1.10 (m, 3H), 1.05-0.80 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H)；
比旋光度：［α］_D -2.92 （c 1.06、メタノール、25℃）。 Reference example 3 (7)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.16 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 4.16 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.47 (m, 1H), 3.41-3.24 (m, 4H) , 3.12 (m, 1H), 2.44 (m, 1H), 2.33 (m, 1H), 2.19 (m, 1H), 2.08 (m, 1H), 2.03-1.89 (m, 2H), 1.84-1.62 (m , 4H), 1.50 (m, 1H), 1.40-1.10 (m, 3H), 1.05-0.80 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H);
Specific rotation: [α] _D -2.92 (c 1.06, methanol, 25 ° C).

ＴＬＣ：Ｒｆ 0.16（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ4.15 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.71 (m, 1H), 3.52 (m, 1H), 3.42-3.31 (m, 2H), 3.21 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.48-2.32 (m, 2H), 2.23 (m, 1H), 2.14-1.96 (m, 2H), 1.72 (m, 1H), 1.55-1.33 (m, 3H), 1.02-0.92 (m, 9H)；
比旋光度：［α］_D -13.8 （c 1.00、メタノール、28℃）。 Reference example 3 (8)
(3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-2-methylpropyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.16 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 4.15 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.71 (m, 1H), 3.52 (m, 1H), 3.42-3.31 (m, 2H) , 3.21 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.48-2.32 (m, 2H), 2.23 (m, 1H), 2.14-1.96 (m, 2H), 1.72 (m , 1H), 1.55-1.33 (m, 3H), 1.02-0.92 (m, 9H);
Specific rotation: [α] _D -13.8 (c 1.00, methanol, 28 ° C).

ＴＬＣ：Ｒｆ 0.17（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ4.16 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.52 (m, 1H), 3.42-3.25 (m, 3H), 3.17 (m, 1H), 2.49-2.38 (m, 2H), 2.21 (m, 1H), 2.14-1.90 (m, 3H), 1.84-1.61 (m, 5H), 1.55-1.13 (m, 6H), 1.04-0.81 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)；
比旋光度：［α］_D -1.29 （c 1.09、メタノール、26℃）。 Reference example 3 (9)
(3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.17 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 4.16 (d, J = 2.1 Hz, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.52 (m, 1H), 3.42-3.25 (m, 3H) , 3.17 (m, 1H), 2.49-2.38 (m, 2H), 2.21 (m, 1H), 2.14-1.90 (m, 3H), 1.84-1.61 (m, 5H), 1.55-1.13 (m, 6H) , 1.04-0.81 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H);
Specific rotation: [α] _D -1.29 (c 1.09, methanol, 26 ° C).

参考例３で製造した化合物（１２０ｍｇ）のジメチルホルムアミド（１ｍｌ）溶液に、酢酸（５９μｌ）を加えた。反応混合物に水素化トリアセトキシホウ素ナトリウム（１４６ｍｇ）と３−ホルミル−６−フェニルオキシピリジン（８９ｍｇ）を加えた。反応混合物を室温で一晩撹拌した。反応混合物にメタノールを加え、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル→クロロホルム：メタノール＝２５：１）によって精製し、通常の方法で塩酸塩に変換して、以下の物性値を有する本発明化合物（１１８ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.35 (d, J = 2.1 Hz, 1H), 8.12 (dd, J = 8.7, 2.1 Hz, 1H), 7.49-7.40 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.7, 1H), 4.39 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.07-3.93 (m, 1H), 3.82-3.67 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.15(m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60-2.28 (m, 3H), 2.18-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.55 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)；
比旋光度：［α］_D +10.8°（c 1.05、メタノール、24℃）；
ＨＰＬＣ条件
使用したカラム：CHIRALCEL OJ-R、0.46×15cm、DAICEL、OJR0CD-JB026；
使用した流速：0.7ｍＬ／ｍｉｎ；
使用した溶媒
Ａ液：0.1Ｍリン酸二水素カリウム水溶液、Ｂ液：アセトニトリル（Ａ：Ｂ＝７６：２４）；
使用したＵＶ：２２５ｎｍ；
保持時間：11.53ｍｉｎ。 Example 2
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

Acetic acid (59 μl) was added to a solution of the compound (120 mg) produced in Reference Example 3 in dimethylformamide (1 ml). To the reaction mixture were added sodium triacetoxyborohydride (146 mg) and 3-formyl-6-phenyloxypyridine (89 mg). The reaction mixture was stirred overnight at room temperature. The reaction mixture was added with methanol and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate → chloroform: methanol = 25: 1) and converted into a hydrochloride by a conventional method to give the compound of the present invention (118 mg) having the following physical data. Was.
TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.35 (d, J = 2.1 Hz, 1H), 8.12 (dd, J = 8.7, 2.1 Hz, 1H), 7.49-7.40 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.7, 1H), 4.39 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.07- 3.93 (m, 1H), 3.82-3.67 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.15 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60- 2.28 (m, 3H), 2.18-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.55 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H);
Specific rotation: [α] _D + 10.8 ° (c 1.05, methanol, 24 ° C.);
Column using HPLC conditions: CHIRALCEL OJ-R, 0.46 × 15 cm, DAICEL, OJR0CD-JB026;
Flow rate used: 0.7 mL / min;
Solvent A used: 0.1 M aqueous solution of potassium dihydrogen phosphate, solution B: acetonitrile (A: B = 76: 24);
UV used: 225 nm;
Retention time: 11.53min.

Example 2 (1) to 2 (59)
The same operation as in Example 2 was carried out using the corresponding aldehyde derivative instead of 3-formyl-6-phenyloxypyridine to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.36（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.45 (d, J = 8.7 Hz, 2H), 7.00-6.96 (m, 6H), 4.27 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.94-3.69 (m, 2H), 3.79 (s, 3H), 3.60-3.05 (m, 5H), 2.50-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H)。 Example 2 (1)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.45 (d, J = 8.7 Hz, 2H), 7.00-6.96 (m, 6H), 4.27 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.94 -3.69 (m, 2H), 3.79 (s, 3H), 3.60-3.05 (m, 5H), 2.50-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00 -0.93 (m, 9H).

ＴＬＣ：Ｒｆ 0.41（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.51 (d, J = 8.4 Hz, 2H), 7.28 (t, J = 8.4 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 6.75 (m, 1H), 6.61-6.57 (m, 2H), 4.32 (s, 2H), 4.14 (d J = 2.1 Hz, 1H), 3.99-3.73 (m, 2H), 3.77 (s, 3H), 3.60-3.10 (m, 5H), 2.55-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H)。 Example 2 (2)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.51 (d, J = 8.4 Hz, 2H), 7.28 (t, J = 8.4 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 6.75 (m, 1H) ), 6.61-6.57 (m, 2H), 4.32 (s, 2H), 4.14 (d J = 2.1 Hz, 1H), 3.99-3.73 (m, 2H), 3.77 (s, 3H), 3.60-3.10 (m , 5H), 2.55-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H).

ＴＬＣ：Ｒｆ 0.33（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.50 (d, J = 8.7 Hz, 2H), 7.17-7.03 (m, 6H), 4.30 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.97-3.71 (m, 2H), 3.60-3.10 (m, 5H), 2.55-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H)。 Example 2 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-fluorophenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.33 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.50 (d, J = 8.7 Hz, 2H), 7.17-7.03 (m, 6H), 4.30 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.97 -3.71 (m, 2H), 3.60-3.10 (m, 5H), 2.55-1.95 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H) .

ＴＬＣ：Ｒｆ 0.31（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 9.3 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 9.3 Hz, 2H), 4.32 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.98-3.72 (m, 2H), 3.60-3.10 (m, 5H), 2.55-2.00 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H)。 Example 2 (4)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.31 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 9.3 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 9.3 Hz, 2H), 4.32 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.98-3.72 (m, 2H), 3.60-3.10 (m, 5H), 2.55-2.00 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.93 (m, 9H).

ＴＬＣ：Ｒｆ 0.57（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.87 (d, J = 8.4 Hz, 2H), 7.83-7.72 (m, 4H), 7.67 (m, 1H), 7.59-7.48 (m, 2H), 4.48 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.59-3.37 (m, 3H), 3.20 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60-2.28 (m, 3H), 2.14 (m, 1H), 2.00 (m, 1H), 1.70 (m, 1H), 1.52-1.23 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (5)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylcarbonyl) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.57 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.87 (d, J = 8.4 Hz, 2H), 7.83-7.72 (m, 4H), 7.67 (m, 1H), 7.59-7.48 (m, 2H), 4.48 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.59-3.37 (m, 3H), 3.20 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60-2.28 (m, 3H), 2.14 (m, 1H), 2.00 (m, 1H), 1.70 (m, 1H), 1.52-1.23 (m, 3H), 0.99 ( d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.32（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.62-7.40 (m, 4H), 7.40-7.18 (m, 5H), 5.81 (s, 1H), 4.32 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.73 (m, 1H), 3.55-3.38 (m, 3H), 3.13 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.52-2.33 (m, 2H), 2.24 (m, 1H), 2.09 (m, 1H), 1.98 (m, 1H), 1.67 (m, 1H), 1.50-1.25 (m, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H)。 Example 2 (6)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.32 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.62-7.40 (m, 4H), 7.40-7.18 (m, 5H), 5.81 (s, 1H), 4.32 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.73 (m, 1H), 3.55-3.38 (m, 3H), 3.13 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.52-2.33 (m, 2H), 2.24 (m, 1H), 2.09 (m, 1H), 1.98 (m, 1H), 1.67 (m, 1H), 1.50-1.25 (m, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.47（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.59 (d, J = 8.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.99 (m, 1H), 3.85-3.35 (m, 12H), 3.23 (m, 1H), 3.19 (dd, J = 9.3, 1.8 Hz, 1H), 2.55-2.41 (m, 2H), 2.32 (m, 1H), 2.12 (m, 1H), 2.01 (m, 1H), 1.68 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (7)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.47 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.59 (d, J = 8.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.99 (m, 1H), 3.85-3.35 (m, 12H), 3.23 (m, 1H), 3.19 (dd, J = 9.3, 1.8 Hz, 1H), 2.55-2.41 (m, 2H), 2.32 (m, 1H), 2.12 (m, 1H), 2.01 (m, 1H), 1.68 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.19（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.58 (d, J = 2.7, 0.6 Hz, 1H), 8.17 (dd, J = 9.0, 2.7 Hz, 1H), 7.89 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 9.0 Hz, 2H), 7.31 (d, J = 9.0 Hz, 2H), 4.40 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.42 (m, 3H), 3.30-3.16 (m, 2H), 2.76 (s, 3H), 2.64-2.32 (m, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.48-1.26 (m, 3H), 1.00 (d, J = 6.3 Hz, 3H), 0.98 (d, J = 6.3 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 2 (8)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridin-3-yloxy) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.19 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.58 (d, J = 2.7, 0.6 Hz, 1H), 8.17 (dd, J = 9.0, 2.7 Hz, 1H), 7.89 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 9.0 Hz, 2H), 7.31 (d, J = 9.0 Hz, 2H), 4.40 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.42 (m, 3H), 3.30-3.16 (m, 2H), 2.76 (s, 3H), 2.64-2.32 (m, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.48-1.26 (m, 3H), 1.00 (d, J = 6.3 Hz, 3H), 0.98 (d, J = 6.3 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H) .

ＴＬＣ：Ｒｆ 0.54（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.56 (m, 1H), 8.45 (m, 1H), 7.81-7.68 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.58-3.42 (m, 3H), 3.28-3.16 (m, 2H), 2.64-2.26 (m, 3H), 2.20-1.92 (m, 2H), 1.68 (m, 1H), 1.52-1.28 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 2 (9)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) phenylmethyl) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.54 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.56 (m, 1H), 8.45 (m, 1H), 7.81-7.68 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.58-3.42 (m, 3H), 3.28- 3.16 (m, 2H), 2.64-2.26 (m, 3H), 2.20-1.92 (m, 2H), 1.68 (m, 1H), 1.52-1.28 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.69（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ7.75 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.38 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.14-3.94 (m, 2H), 3.78 (m, 1H), 3.58-3.40 (m, 4H), 3.30-3.00 (m, 4H), 2.68-2.36 (m, 3H), 2.20-1.58 (m, 8H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 6,9 Hz, 3H)。 Example 2 (10)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxypiperidin-1-ylmethyl) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.69 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 7.75 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.38 (s, 2H), 4.14 (d , J = 2.1 Hz, 1H), 4.14-3.94 (m, 2H), 3.78 (m, 1H), 3.58-3.40 (m, 4H), 3.30-3.00 (m, 4H), 2.68-2.36 (m, 3H ), 2.20-1.58 (m, 8H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 6,9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.65（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.32 (m, 1H), 4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60-3.42 (m, 3H), 3.36-3.16 (m, 2H), 2.64-2.42 (m, 3H), 2.49 (s, 3H), 2.44 (s, 3H), 2.18-1.22 (m, 16H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (11)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.65 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 4.32 (m, 1H), 4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60 -3.42 (m, 3H), 3.36-3.16 (m, 2H), 2.64-2.42 (m, 3H), 2.49 (s, 3H), 2.44 (s, 3H), 2.18-1.22 (m, 16H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.85 (s, 3H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.28-3.16 (m, 2H), 2.64-2.32 (m, 3H), 2.44 (s, 3H), 2.40 (s, 3H), 2.18-1.92 (m, 2H), 1.70 (m, 1H), 1.48-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H) 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (12)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1, 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.50 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.85 (s, 3H), 3.76 (m, 1H), 3.60 -3.44 (m, 3H), 3.28-3.16 (m, 2H), 2.64-2.32 (m, 3H), 2.44 (s, 3H), 2.40 (s, 3H), 2.18-1.92 (m, 2H), 1.70 (m, 1H), 1.48-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H) 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.91 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.38 (m, 3H), 3.28-3.18 (m, 2H), 2.56-1.92 (m, 5H), 1.70 (m, 1H), 1.54-1.28 (m, 3H), 1.00 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (13)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.91 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.38 (m, 3H), 3.28 -3.18 (m, 2H), 2.56-1.92 (m, 5H), 1.70 (m, 1H), 1.54-1.28 (m, 3H), 1.00 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 9.0 Hz, 2H), 7.32 (d, J = 9.0 Hz, 2H), 7.05 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.40 (m, 3H), 3.28- 3.10 (m, 2H), 2.52-1.92 (m, 5H), 2.47 (s, 3H), 1.70 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.86 (m, 9H)。 Example 2 (14)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylthiophenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.45 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 9.0 Hz, 2H), 7.32 (d, J = 9.0 Hz, 2H), 7.05 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.40 (m, 3H), 3.28 -3.10 (m, 2H), 2.52-1.92 (m, 5H), 2.47 (s, 3H), 1.70 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.86 (m, 9H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.24-7.18 (m, 4H), 4.39 (s, 2H), 4.14 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.46 (m, 3H), 3.28-3.10 (m, 2H), 3.12 (s, 3H), 2.54- 1.94 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.02-0.86 (m, 9H)。 Example 2 (15)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.24-7.18 (m, 4H), 4.39 (s, 2H), 4.14 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.46 (m, 3H), 3.28-3.10 (m, 2H), 3.12 (s, 3H), 2.54- 1.94 (m, 5H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.02-0.86 (m, 9H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.73 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 9.0 Hz, 2H), 7.21 (d, J = 9.0 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.38 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.40 (m, 3H), 3.28- 3.14 (m, 2H), 2.54-2.26 (m, 3H), 2.20-1.90 (m, 2H), 1.66 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.84 (m, 9H)。 Example 2 (16)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-cyanophenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.73 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 9.0 Hz, 2H), 7.21 (d, J = 9.0 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.38 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.40 (m, 3H), 3.28 -3.14 (m, 2H), 2.54-2.26 (m, 3H), 2.20-1.90 (m, 2H), 1.66 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.84 (m, 9H) .

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.50-7.34 (m, 7H), 7.30 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.56-3.36 (m, 3H), 3.24-3.08 (m, 2H), 2.50-2.18 (m, 3H), 2.18-1.94 (m, 2H), 1.68 (m , 1H), 1.50-1.28 (m, 3H), 1.10-0.88 (m, 9H)。 Example 2 (17)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylthio) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.50-7.34 (m, 7H), 7.30 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.56-3.36 (m, 3H), 3.24-3.08 (m, 2H), 2.50-2.18 (m, 3H), 2.18-1.94 (m, 2H), 1.68 (m, 1H), 1.50-1.28 (m, 3H), 1.10-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.70（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.31 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.48 (m, 3H), 3.38-3.18 (m, 2H), 2.70-2.30 (m, 3H), 2.44 (s, 3H), 2.36 (s, 3H), 2.20-1.94 (m, 2H), 1.68 (m, 1H), 1.50-1.26 (m, 3H), 1.02-0.84 (m, 9H)。 Example 2 (18)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.70 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.31 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.48 (m, 3H), 3.38-3.18 (m, 2H), 2.70-2.30 (m, 3H), 2.44 (s, 3H), 2.36 (s, 3H), 2.20-1.94 (m, 2H), 1.68 (m, 1H), 1.50-1.26 (m, 3H), 1.02-0.84 (m, 9H).

ＴＬＣ：Ｒｆ 0.72（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.47 (d, J = 9.0 Hz, 2H), 7.41 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.38-3.18 (m, 2H), 3.04 (s, 3H), 2.68-2.36 (m, 3H), 2.41 (s, 3H), 2.39 (s, 3H), 2.20-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.30 (m, 3H), 1.02-0.88 (m, 9H)。 Example 2 (19)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylsulfonylaminophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.72 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.47 (d, J = 9.0 Hz, 2H), 7.41 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H) ), 4.02 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.38-3.18 (m, 2H), 3.04 (s, 3H), 2.68-2.36 (m, 3H), 2.41 (s, 3H), 2.39 (s, 3H), 2.20-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.30 (m, 3H), 1.02-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.12（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.62-3.48 (m, 3H), 3.40-3.18 (m, 6H), 2.95 (s, 6H), 2.64 (m, 1H), 2.49 (s, 3 H), 2.42-2.36 (m, 2H), 2.41 (s, 3H), 2.18-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.32 (m, 3H), 1.08-0.90 (m, 9H)。 Example 2 (20)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (N , N-Dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane / 3 hydrochloride

TLC: Rf 0.12 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.02 (m, 1H), 3.76 (m, 1H), 3.62-3.48 (m, 3H), 3.40-3.18 (m, 6H), 2.95 (s, 6H), 2.64 (m, 1H), 2.49 ( s, 3H), 2.42-2.36 (m, 2H), 2.41 (s, 3H), 2.18-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.32 (m, 3H), 1.08-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.40-3.18 (m, 6H), 2.66 (m, 1H), 2.54-2.38 (m, 2H), 2.49 (s, 3H), 2.42 (s, 3H), 2.20-1.94 (m, 2H), 1.82-1.62 (m, 5H), 1.50-1.30 (m, 3H), 1.02-0.88 (m, 9H)。 Example 2 (21)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine-1- Ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.40-3.18 (m, 6H), 2.66 (m, 1H), 2.54-2.38 (m, 2H), 2.49 (s, 3H), 2.42 (s, 3H), 2.20-1.94 (m, 2H), 1.82-1.62 (m, 5H), 1.50-1.30 (m, 3H), 1.02-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.26（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.58 (m, 1H), 7.81-7.71 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.62-3.40 (m, 3H), 3.30-3.16 (m, 2H), 2.66-2.38 (m, 3H), 2.66 (s, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.50-1.28 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 2 (22)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridin-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.26 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ8.58 (m, 1H), 7.81-7.71 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.62-3.40 (m, 3H), 3.30-3.16 (m, 2H), 2.66-2.38 (m, 3H), 2.66 (s, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.50-1.28 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.46 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.53-3.42 (m, 3H), 3.23- 3.11 (m, 2H), 2.50-1.97 (m, 6H), 1.70 (m, 1H), 1.39-1.30 (m, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 2 (23)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.48 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.46 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.53-3.42 (m, 3H), 3.23 -3.11 (m, 2H), 2.50-1.97 (m, 6H), 1.70 (m, 1H), 1.39-1.30 (m, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.41 (m, 1H), 8.18 (m, 1H), 7.13-6.99 (m, 5H), 4.40 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.53-3.45 (m, 3H), 3.24 (m, 1H), 3.19 (dd, J = 9.5, 2.0 Hz, 1H), 2. 59-2.39 (m, 3H), 2.15-1.95 (m, 2H), 1.70 (m, 1H), 1.40-1.31 (m, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H)。 Example 2 (24)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6- (4-methoxyphenyloxy) pyridin-3-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.41 (m, 1H), 8.18 (m, 1H), 7.13-6.99 (m, 5H), 4.40 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H) , 4.00 (m, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.53-3.45 (m, 3H), 3.24 (m, 1H), 3.19 (dd, J = 9.5, 2.0 Hz, 1H ), 2.59-2.39 (m, 3H), 2.15-1.95 (m, 2H), 1.70 (m, 1H), 1.40-1.31 (m, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.29（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ8.00 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.79 (m, 1H), 3.64-3.50 (m, 3H), 3.29-3.19 (m, 2H), 2.59-2.35 (m, 3H), 2.58 (s, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.72 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (25)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (methylaminosulfonyl) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.29 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 8.00 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H) ), 4.05 (m, 1H), 3.79 (m, 1H), 3.64-3.50 (m, 3H), 3.29-3.19 (m, 2H), 2.59-2.35 (m, 3H), 2.58 (s, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.72 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.21（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.98 (d, J = 8.5 Hz, 2H), 7.75 (d, J = 8.5 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.69 (t, J = 6.0 Hz, 2H), 3.61-3.51 (m, 3H), 3.23-3.17 (m, 4H), 2.87 (s, 3H) , 2.58-2.44 (m, 3H),2.48 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 2 (26)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N-methyl- N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.21 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.98 (d, J = 8.5 Hz, 2H), 7.75 (d, J = 8.5 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.69 (t, J = 6.0 Hz, 2H), 3.61-3.51 (m, 3H), 3.23-3.17 (m, 4H), 2.87 (s, 3H), 2.58-2.44 (m, 3H), 2.48 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.20（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.63-3.51 (m, 3H), 3.56 (t, J = 6.0 Hz, 2H), 3.34-3.29 (m, 1H), 3.20 (dd, J = 9.5, 2.0 Hz, 1H), 3.01 (t, J = 6.0 Hz, 2H), 2.59-2.43 (m, 3H),2.47 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 H z, 3 H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (27)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethyl Aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.20 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.63-3.51 (m, 3H), 3.56 (t, J = 6.0 Hz, 2H), 3.34-3.29 (m, 1H), 3.20 (dd, J = 9.5, 2.0 Hz, 1H), 3.01 (t, J = 6.0 Hz, 2H), 2.59-2.43 (m, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H ), 2.02 (m, 1H), 1.71 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H) , 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.35（酢酸エチル：メタノール＝２：１）；
ＮＭＲ（CD₃OD）：δ7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.79 (m, 1H), 3.61-3.49 (m, 3H), 3.34-3.29 (m, 1H), 3.20 (dd, J = 9.5, 2.0 Hz, 1H), 3.13 ( s, 3H), 3.04 (s, 3H), 2.55-2.34 (m, 3H), 2.42 (s, 3H), 2.39 (s, 3H), 2.18 (m, 1H), 2.02 (m, 1H), 1.73 (m, 1H), 1.41-1.34 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (t, J = 7 .0 Hz , 3H)。 Example 2 (28)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N- Dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.35 (ethyl acetate: methanol = 2: 1);
NMR (CD ₃ OD): δ 7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H) ), 4.05 (m, 1H), 3.79 (m, 1H), 3.61-3.49 (m, 3H), 3.34-3.29 (m, 1H), 3.20 (dd, J = 9.5, 2.0 Hz, 1H), 3.13 ( s, 3H), 3.04 (s, 3H), 2.55-2.34 (m, 3H), 2.42 (s, 3H), 2.39 (s, 3H), 2.18 (m, 1H), 2.02 (m, 1H), 1.73 (m, 1H), 1.41-1.34 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.33（酢酸エチル：メタノール＝２：１）；
ＮＭＲ（CD₃OD）：δ8.06 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.10-4.01 (m, 3H), 3.88-3.76 (m, 3H), 3.61-3.53 (m, 5H), 3.37-3.19 (m, 8H), 2.59-2.37 (m, 3H), 2.48 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.40-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 2 (29)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (morpholine -4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.33 (ethyl acetate: methanol = 2: 1);
NMR (CD ₃ OD): δ 8.06 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H) ), 4.10-4.01 (m, 3H), 3.88-3.76 (m, 3H), 3.61-3.53 (m, 5H), 3.37-3.19 (m, 8H), 2.59-2.37 (m, 3H), 2.48 (s , 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.40-1.35 (m, 3H), 0.99 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.72 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.79 (m, 1H), 3.66-3.46 (m, 7H), 3.25 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.65-2.35 (m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.16 (m, 1H), 2.09-1.87 (m, 5H), 1.70 (m, 1H), 1.53-1.30 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (30)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine-1- Ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.72 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.05 (m, 1H), 3.79 (m, 1H), 3.66-3.46 (m, 7H), 3.25 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.65-2.35 ( m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.16 (m, 1H), 2.09-1.87 (m, 5H), 1.70 (m, 1H), 1.53-1.30 (m, 3H) , 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.39（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.74 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.14 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.58-3.42 (m, 3H), 3.25- 3.14 (m, 2H), 2.80 (s, 3H), 2.55-2.38 (m, 2H), 2.29 (m, 1H), 2.15 (m, 1H), 2.01 (m, 1H), 1.70 (m, 1H), 1.50-1.27 (m, 3H), 1.04-0.90 (m, 9H)。 Example 2 (31)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.39 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.74 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.14 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.58-3.42 (m, 3H), 3.25 -3.14 (m, 2H), 2.80 (s, 3H), 2.55-2.38 (m, 2H), 2.29 (m, 1H), 2.15 (m, 1H), 2.01 (m, 1H), 1.70 (m, 1H ), 1.50-1.27 (m, 3H), 1.04-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.31（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 4.06 (m, 1H), 3.79 (m, 1H), 3.64-3.46 (m, 3H), 3.29-3.14 (m, 2H), 2.73 (s, 6H), 2.59-2.44 (m, 2H), 2.47 (s, 3H), 2.39 (s, 3H), 2.35 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.51-1.26 (m, 3H), 1.05-0.89 (m, 9H)。 Example 2 (32)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N- Dimethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.31 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H) ), 4.06 (m, 1H), 3.79 (m, 1H), 3.64-3.46 (m, 3H), 3.29-3.14 (m, 2H), 2.73 (s, 6H), 2.59-2.44 (m, 2H), 2.47 (s, 3H), 2.39 (s, 3H), 2.35 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.51-1.26 (m, 3H) , 1.05-0.89 (m, 9H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.74-3.68 (m, 4H), 3.64-3.48 (m, 3H), 3.28-3.14 (m, 2H), 3.05-2.98 (m, 4H), 2.59-2.44 (m, 2H), 2.47 (s, 3H), 2.39 (s, 3H), 2.35 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.52-1.30 (m, 3H), 1.05-0.90 (m, 9H)。 Example 2 (33)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine-4- Ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.06 (m, 1H), 3.80 (m, 1H), 3.74-3.68 (m, 4H), 3.64-3.48 (m, 3H), 3.28-3.14 (m, 2H), 3.05-2.98 (m, 4H) ), 2.59-2.44 (m, 2H), 2.47 (s, 3H), 2.39 (s, 3H), 2.35 (m, 1H), 2.17 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.52-1.30 (m, 3H), 1.05-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.22（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.92 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.60-3.38 (m, 3H), 3.28-3.10 (m, 2H), 2.60-2.26 (m, 3H), 2.20-1.88 (m, 2H), 1.68 (m, 1H), 1.54-1.22 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (34)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.22 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.92 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.60-3.38 (m, 3H), 3.28 -3.10 (m, 2H), 2.60-2.26 (m, 3H), 2.20-1.88 (m, 2H), 1.68 (m, 1H), 1.54-1.22 (m, 3H), 1.00 (d, J = 6.6 Hz , 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.24（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.85 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.56-3.42 (m, 3H), 3.26-3.18 (m, 2H), 2.92 (s, 3H), 2.60-2.28 (m, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (35)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.24 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.85 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.56-3.42 (m, 3H), 3.26 -3.18 (m, 2H), 2.92 (s, 3H), 2.60-2.28 (m, 3H), 2.18-1.94 (m, 2H), 1.70 (m, 1H), 1.50-1.30 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.46（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.41 (s, 4H), 4.34 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.65-3.50 (m, 3H), 3.34 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.66 (m, 1H), 2.55-2.42 (m, 2H), 2.47 (s, 3H), 2.45 (s, 3H), 2.40 (s, 3H), 2.14 (m, 1H), 2.01 (m, 1H), 1.69 (m, 1H), 1.52-1.30 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (36)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylphenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.46 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.41 (s, 4H), 4.34 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.65 -3.50 (m, 3H), 3.34 (m, 1H), 3.21 (dd, J = 9.6, 2.1 Hz, 1H), 2.66 (m, 1H), 2.55-2.42 (m, 2H), 2.47 (s, 3H ), 2.45 (s, 3H), 2.40 (s, 3H), 2.14 (m, 1H), 2.01 (m, 1H), 1.69 (m, 1H), 1.52-1.30 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.63-3.48 (m, 3H), 3.32-3.17 (m, 2H), 3.29 (q, J = 7.2 Hz, 4H), 2.54-2.13 (m, 4H), 2.45 (s, 3H), 2.39 (s, 3H), 2.02 (m, 1H), 1.72 (m, 1H), 1.52-1.33 (m, 3H), 1.15 (t, J = 7.2 Hz, 6H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t,J = 6.9 Hz, 3H)。 Example 2 (37)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N- Diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.35 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H) ), 4.06 (m, 1H), 3.80 (m, 1H), 3.63-3.48 (m, 3H), 3.32-3.17 (m, 2H), 3.29 (q, J = 7.2 Hz, 4H), 2.54-2.13 ( m, 4H), 2.45 (s, 3H), 2.39 (s, 3H), 2.02 (m, 1H), 1.72 (m, 1H), 1.52-1.33 (m, 3H), 1.15 (t, J = 7.2 Hz , 6H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.22（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.11-3.94 (m, 3H), 3.80 (m, 1H), 3.65-3.48 (m, 5H), 3.34-3.18 (m, 4H), 2.91 (s, 3H), 2.86-2.70 (m, 2H), 2.68-2.36 (m, 3H), 2.49 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.50-1.27 (m, 3H), 1.05-0.90 (m, 9H)。 Example 2 (38)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4-methylpiperazine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.22 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H) ), 4.11-3.94 (m, 3H), 3.80 (m, 1H), 3.65-3.48 (m, 5H), 3.34-3.18 (m, 4H), 2.91 (s, 3H), 2.86-2.70 (m, 2H ), 2.68-2.36 (m, 3H), 2.49 (s, 3H), 2.40 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.50-1.27 ( m, 3H), 1.05-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.63-7.48 (m, 5H), 4.33 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.10 (m, 1H), 3.83 (m, 1H), 3.66-3.45 (m, 3H), 3.29-3.16 (m, 2H), 2.62-2.32 (m, 3H), 2.44 (s, 3H), 2.17 (m, 1H), 2.01 (m, 1H), 1.71 (m, 1H ), 1.52-1.11 (m, 3H), 1.05-0.88 (m, 9H)。 Example 2 (39)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (5-chloro-3-methyl-1-phenylpyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.63-7.48 (m, 5H), 4.33 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.10 (m, 1H), 3.83 (m, 1H) , 3.66-3.45 (m, 3H), 3.29-3.16 (m, 2H), 2.62-2.32 (m, 3H), 2.44 (s, 3H), 2.17 (m, 1H), 2.01 (m, 1H), 1.71 (m, 1H), 1.52-1.11 (m, 3H), 1.05-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.39（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.66-7.57 (m, 4H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.88-3.39 (m, 12H), 3.25 (m, 1H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 2.65-2.27 (m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.17 (m, 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.54-1.27 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 2 (40)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine-4- Ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.39 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.66-7.57 (m, 4H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.88-3.39 (m, 12H), 3.25 (m, 1H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 2.65-2.27 (m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.17 (m , 1H), 2.02 (m, 1H), 1.71 (m, 1H), 1.54-1.27 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H) , 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.74 (t, J = 5.7 Hz, 2H), 3.64-3.48 (m, 3H), 3.54 (t, J = 5.7 Hz, 2H), 3.30-3.16 (m, 2H), 2.64-2.34 (m, 3H), 2.45 (s, 3H), 2.41 (s, 3H), 2.22-1.92 (m, 2H), 1.72 (m, 1H), 1.52-1.26 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 2 (41)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethyl Aminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H) ), 4.04 (m, 1H), 3.80 (m, 1H), 3.74 (t, J = 5.7 Hz, 2H), 3.64-3.48 (m, 3H), 3.54 (t, J = 5.7 Hz, 2H), 3.30 -3.16 (m, 2H), 2.64-2.34 (m, 3H), 2.45 (s, 3H), 2.41 (s, 3H), 2.22-1.92 (m, 2H), 1.72 (m, 1H), 1.52-1.26 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.19（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.93 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.18-7.08 (m, 4H), 4.36 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.00 (m, 1H), 3.80-3.70 (m, 3H), 3.54-3.42 (m, 3H), 3.38 (t, J = 6.3 Hz, 2H), 3.26-3. 18 (m, 2H), 2.98 (s, 6H), 2.60-2.30 (m, 3H), 2.18-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.90 (m, 9H)。 Example 2 (42)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2- (N, N-dimethylamino) Ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.19 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.93 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.18-7.08 (m, 4H), 4.36 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.00 (m, 1H), 3.80-3.70 (m, 3H), 3.54-3.42 (m, 3H), 3.38 (t, J = 6.3 Hz, 2H), 3.26- 3.18 (m, 2H), 2.98 (s, 6H), 2.60-2.30 (m, 3H), 2.18-1.96 (m, 2H), 1.68 (m, 1H), 1.50-1.30 (m, 3H), 1.00-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.31（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.74 (m, 1H), 8.62 (d, J = 5.4 Hz, 1H), 8.24 (m, 1H), 8.14 (m, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.30-3.16 (m, 2H), 2.60 (m, 1H), 2.50-2.40 (m, 2H), 2.26-1.86 (m, 2H), 1.66 (m, 1H), 1.50-1.30 (m, 3H), 1.02-0.88 (m, 9H)。 Example 2 (43)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-3-yloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.31 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.74 (m, 1H), 8.62 (d, J = 5.4 Hz, 1H), 8.24 (m, 1H), 8.14 (m, 1H), 7.76 (d, J = 8.4 Hz) , 2H), 7.34 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60 -3.44 (m, 3H), 3.30-3.16 (m, 2H), 2.60 (m, 1H), 2.50-2.40 (m, 2H), 2.26-1.86 (m, 2H), 1.66 (m, 1H), 1.50 -1.30 (m, 3H), 1.02-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.24- 3.08 (m, 2H), 2.56-1.92 (m, 5H), 1.70 (m, 1H), 1.50-1.26 (m, 3H), 1.08-0.90 (m, 9H)。 Example 2 (44)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.42 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.07 (d, J) = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.24 -3.08 (m, 2H), 2.56-1.92 (m, 5H), 1.70 (m, 1H), 1.50-1.26 (m, 3H), 1.08-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.49 (d, J = 9.0 Hz, 2H), 7.20 (d, J = 9.0 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.36 (m, 3H), 3.26- 3.08 (m, 2H), 2.52-1.82 (m, 5H), 2.33 (s, 3H), 1.68 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.86 (m, 9H)。 Example 2 (45)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.49 (d, J = 9.0 Hz, 2H), 7.20 (d, J = 9.0 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.58-3.36 (m, 3H), 3.26 -3.08 (m, 2H), 2.52-1.82 (m, 5H), 2.33 (s, 3H), 1.68 (m, 1H), 1.50-1.28 (m, 3H), 1.02-0.86 (m, 9H).

ＴＬＣ：Ｒｆ 0.63（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.56 (m, 1H), 7.33-7.16 (m, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.62-3.44 (m, 3H), 3.28-3.16 (m, 2H), 2.62-1.84 (m, 5H), 2.39 (s, 3H), 2.28 (s, 3H), 1.72 (m, 1H), 1.54-1.28 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 2 (46)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (2,4-difluorophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.63 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ7.56 (m, 1H), 7.33-7.16 (m, 2H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H) , 3.80 (m, 1H), 3.62-3.44 (m, 3H), 3.28-3.16 (m, 2H), 2.62-1.84 (m, 5H), 2.39 (s, 3H), 2.28 (s, 3H), 1.72 (m, 1H), 1.54-1.28 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (t, J = 7.2 Hz, 3H) .

ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.52 (m, 1H), 8.01 (m, 1H), 7.81 (m, 1H), 7.41 (m, 1H), 4.33 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.26-3.12 (m, 2H), 2.68 (s, 3H), 2.58-2.24 (m, 3H), 2.41 (s, 3H), 2.18 (m, 1H), 2.04 (m, 1H), 1.70 (m, 1H), 1.54-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (47)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (pyridin-2-yl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.52 (m, 1H), 8.01 (m, 1H), 7.81 (m, 1H), 7.41 (m, 1H), 4.33 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.26-3.12 (m, 2H), 2.68 (s, 3H), 2.58-2.24 (m , 3H), 2.41 (s, 3H), 2.18 (m, 1H), 2.04 (m, 1H), 1.70 (m, 1H), 1.54-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.18（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.49 (m, 3H), 3.30-3.17 (m, 2H), 2.94 (s, 3H), 2.59 (m, 1H), 2.51-2.36 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.52-1.27 (m, 3H), 1.05-0.91 (m, 9H)。 Example 2 (48)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.18 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.49 (m, 3H), 3.30-3.17 (m, 2H), 2.94 (s, 3H), 2.59 (m, 1H), 2.51- 2.36 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.52-1.27 (m, 3H) , 1.05-0.91 (m, 9H).

ＴＬＣ：Ｒｆ 0.44（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.44 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 4.38 (m, 1H), 4.27 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 3.96 (m, 1H), 3.70 (m, 1H), 3.58-3.36 (m, 3H), 3.26-3.08 (m, 2H), 2.54-1.26 (m, 19H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (49)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4-cyclohexyloxyphenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.44 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.44 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 4.38 (m, 1H), 4.27 (s, 2H), 4.14 (d , J = 2.1 Hz, 1H), 3.96 (m, 1H), 3.70 (m, 1H), 3.58-3.36 (m, 3H), 3.26-3.08 (m, 2H), 2.54-1.26 (m, 19H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.33（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.47 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.64 (m, 1H), 4.29 (s, 2H), 4.14 (d, J = 2.4 Hz, 1H), 4.04-3.86 (m, 3H), 3.80-3.36 (m, 6H), 3.26-3.08 (m, 2H), 2.52-1.90 (m, 7H), 1.80-1.58 (m, 3H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (50)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3,4,5,6-tetrahydropyran-4- Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.33 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.47 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.64 (m, 1H), 4.29 (s, 2H), 4.14 (d , J = 2.4 Hz, 1H), 4.04-3.86 (m, 3H), 3.80-3.36 (m, 6H), 3.26-3.08 (m, 2H), 2.52-1.90 (m, 7H), 1.80-1.58 (m , 3H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.77 (s, 3H), 3.77 (m, 1H), 3.58-3.40 (m, 3H), 3.26-3.10 (m, 2H), 2.54-2.22 (m, 3H), 2.20-1.90 (m, 2H), 1.66 (m, 1H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (51)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.37 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.77 (s, 3H), 3.77 (m , 1H), 3.58-3.40 (m, 3H), 3.26-3.10 (m, 2H), 2.54-2.22 (m, 3H), 2.20-1.90 (m, 2H), 1.66 (m, 1H), 1.50-1.26 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.44（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.91 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 4.42 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 4.03 (m 1H), 3.90-3.72 (m, 2H), 3.56-3.43 (m, 3H), 3.25 (m, 1H), 3.18 (dd, J = 9.6, 2.0 Hz, 1H), 2.53-2.4 0 (m, 2H), 2.30 (m, 1H), 2.14 (m, 1H), 2.06-1.67 (m, 8H), 1.50-1.33 (m, 7H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H)。 Example 2 (52)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.44 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.91 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 4.42 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H) ), 4.03 (m 1H), 3.90-3.72 (m, 2H), 3.56-3.43 (m, 3H), 3.25 (m, 1H), 3.18 (dd, J = 9.6, 2.0 Hz, 1H), 2.53-2.4 0 (m, 2H), 2.30 (m, 1H), 2.14 (m, 1H), 2.06-1.67 (m, 8H), 1.50-1.33 (m, 7H), 0.98 (d, J = 6.6 Hz, 3H) , 0.96 (d, J = 6.6 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.34（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.61-7.57 (m, 4H), 7.14 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.14 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.62-3.45 (m, 7H), 3.24(m, 1H), 3.19 (dd, J = 9.6, 2.0 Hz, 1H), 2.56-2.29 (m, 3H), 2.15-1.89 (m, 6H), 1.70 (m, 1H), 1.40-1.33 (m, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 2 (53)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.34 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.61-7.57 (m, 4H), 7.14 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.14 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.62-3.45 (m, 7H), 3.24 (m, 1H), 3.19 (dd, J = 9.6, 2.0 Hz, 1H), 2.56-2.29 (m, 3H), 2.15-1.89 (m, 6H), 1.70 (m, 1H), 1.40-1.33 (m, 3H), 0.98 (d, J = 6.6 Hz, 3H) , 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.56-7.51 (m, 2H), 7.35-7.28 (m, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.03 (m, 1H), 3.78 (m, 1H), 3.61-3.49 (m, 3H), 3.34 (m, 1H), 3.20 (dd, J = 9.6, 2.0 Hz, 1H), 2.68-2.42 (m, 6H), 2.38 ( s, 3H), 2.17 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.50-1.35 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J - 7.2 Hz, 3H)。 Example 2 (54)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.37 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ7.56-7.51 (m, 2H), 7.35-7.28 (m, 2H), 4.31 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.03 (m, 1H), 3.78 (m, 1H), 3.61-3.49 (m, 3H), 3.34 (m, 1H), 3.20 (dd, J = 9.6, 2.0 Hz, 1H), 2.68-2.42 (m, 6H), 2.38 (s, 3H), 2.17 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H), 1.50-1.35 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 ( d, J = 6.6 Hz, 3H), 0.95 (t, J-7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.13（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.32-7.20 (m, 3H), 7.11-7.08 (m, 2H), 4.45 (t, J = 6.6 Hz, 2H), 4.20 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 3.90 (m, 1H), 3.70-3.48 (m, 3H), 3.42-3.30 (m, 2H), 3.21 (m, 1H), 3.14 (t, J = 6.6 Hz, 2H), 2.76-2.38 (m, 3H), 2.50 (s, 3H), 2.20-1.88 (m, 2H), 1.97 (s, 3H), 1.74 (m, 1H), 1.56-1.34 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.97 (t, J = 6.9 Hz, 3H)。 Example 2 (55)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-phenylethyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.13 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.32-7.20 (m, 3H), 7.11-7.08 (m, 2H), 4.45 (t, J = 6.6 Hz, 2H), 4.20 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 3.90 (m, 1H), 3.70-3.48 (m, 3H), 3.42-3.30 (m, 2H), 3.21 (m, 1H), 3.14 (t, J = 6.6 Hz, 2H ), 2.76-2.38 (m, 3H), 2.50 (s, 3H), 2.20-1.88 (m, 2H), 1.97 (s, 3H), 1.74 (m, 1H), 1.56-1.34 (m, 3H), 1.01 (d, J = 6.6 Hz, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.97 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.13（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.44-7.24 (m, 5H), 5.16 (s, 2H), 4.54 (m, 1H), 4.40-4.20 (m, 2H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.82-3.42 (m, 5H), 3.30-2.88 (m, 3H), 2.64-2.30 (m, 3H), 2.47 (s, 3H), 2.37 (s, 3H), 2.20-1.84 (m, 6H), 1.70 (m, 1H), 1.52-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (56)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidine- 4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.13 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.44-7.24 (m, 5H), 5.16 (s, 2H), 4.54 (m, 1H), 4.40-4.20 (m, 2H), 4.25 (s, 2H), 4.15 ( d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.82-3.42 (m, 5H), 3.30-2.88 (m, 3H), 2.64-2.30 (m, 3H), 2.47 (s, 3H) , 2.37 (s, 3H), 2.20-1.84 (m, 6H), 1.70 (m, 1H), 1.52-1.26 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.47（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.89 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.71 (t, J = 5.7 Hz, 2H), 3.60-3.40 (m, 3H), 3.51 (t, J = 5.7 Hz, 2H), 3.30-3.12 (m, 2H), 2.60-2.24 (m, 3H), 2.22-1.92 (m, 2H), 1.70 (m, 1H), 1.56-1.24 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 2 (57)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.47 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.89 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.09 (d, J) = 9.0 Hz, 2H), 4.37 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.71 (t, J = 5.7 Hz, 2H ), 3.60-3.40 (m, 3H), 3.51 (t, J = 5.7 Hz, 2H), 3.30-3.12 (m, 2H), 2.60-2.24 (m, 3H), 2.22-1.92 (m, 2H), 1.70 (m, 1H), 1.56-1.24 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H ).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.44 (m, 1H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.06-3.64 (m, 4H), 3.60-3.44 (m, 3H), 3.28-3.16 (m, 2H), 3.06-2.92 (m, 2H), 2.90 (s, 3H), 2.64-1.90 (m, 9H), 2.47 (s, 3H), 2.37 (s, 3H), 1.68 (m, 1H), 1.50-1.24 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (58)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonylpiperidine-4) -Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.41 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ4.44 (m, 1H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.06-3.64 (m, 4H), 3.60-3.44 (m, 3H), 3.28-3.16 (m, 2H), 3.06-2.92 (m, 2H), 2.90 (s, 3H), 2.64-1.90 (m, 9H), 2.47 (s, 3H), 2.37 (s, 3H) , 1.68 (m, 1H), 1.50-1.24 (m, 3H), 1.00 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.32（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.36 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 4H), 4.58 (s, 2H), 4.12 (d, J = 2.4 Hz, 1H), 3.73 (s, 2H), 3.47 (m, 1H), 3.30-2.90 (m, 6H), 2.31-1.83 (m, 5H), 1.64 (m, 1H), 1.55-1.23 (m, 3H), 0.97 (d, J = 6.6 Hz, 6H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 2 (59)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane

TLC: Rf 0.32 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.36 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 4H), 4.58 (s, 2H) ), 4.12 (d, J = 2.4 Hz, 1H), 3.73 (s, 2H), 3.47 (m, 1H), 3.30-2.90 (m, 6H), 2.31-1.83 (m, 5H), 1.64 (m, 1H), 1.55-1.23 (m, 3H), 0.97 (d, J = 6.6 Hz, 6H), 0.95 (t, J = 7.5 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（８）で製造した化合物を用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物（110ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.35 (d, J = 2.1 Hz, 1H), 8.12 (dd, J = 8.7, 2.1 Hz, 1H), 7.49-7.40 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.7, 1H), 4.39 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.07-3.93 (m, 1H), 3.82-3.67 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.15(m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60-2.28 (m, 3H), 2.18-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.55 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H)；
比旋光度：［α］_D -10.1 （c 1.04、メタノール、25℃）；
ＨＰＬＣ条件
使用したカラム：CHIRALCEL OJ-R、0.46×15cm、DAICEL、OJR0CD-JB026；
使用した流速：0.7ｍＬ／ｍｉｎ；
使用した溶媒
Ａ液：0.1Ｍリン酸二水素カリウム水溶液、Ｂ液：アセトニトリル（Ａ：Ｂ＝７６：２４）；
使用したＵＶ：２２５ｎｍ；
保持時間：8.65ｍｉｎ。 Example 3
(3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

In the same manner as in Example 2 except that the compound prepared in Reference Example 3 (8) was used instead of the compound prepared in Reference Example 3, the compound of the present invention (110 mg) having the following physical data was obtained. .
TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.35 (d, J = 2.1 Hz, 1H), 8.12 (dd, J = 8.7, 2.1 Hz, 1H), 7.49-7.40 (m, 2H), 7.27 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.7, 1H), 4.39 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.07- 3.93 (m, 1H), 3.82-3.67 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.15 (m, 1H), 3.19 (dd, J = 9.6, 2.1 Hz, 1H), 2.60- 2.28 (m, 3H), 2.18-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.55 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H);
Specific rotation: [α] _D -10.1 (c 1.04, methanol, 25 ° C);
Column using HPLC conditions: CHIRALCEL OJ-R, 0.46 × 15 cm, DAICEL, OJR0CD-JB026;
Flow rate used: 0.7 mL / min;
Solvent A used: 0.1 M aqueous solution of potassium dihydrogen phosphate, solution B: acetonitrile (A: B = 76: 24);
UV used: 225 nm;
Retention time: 8.65 min.

参考例３で製造した化合物の代わりに、参考例３（１）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、［４−（４−ホルミル−３，５−ジメチルピラゾリル）フェニル］−Ｎ，Ｎ−ジメチルカルボキサミドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.62（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.65-7.52 (m, 4H), 4.33 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz, 1H), 3.96-3.72 (m, 2H), 3.64-3.54 (m, 2H), 3.50-3.36 (m, 2H), 3.14 (s, 3H), 3.05 (s, 3H), 2.60-2.42 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.36-2.10 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H)。 Example 4
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (1) was replaced with [4- (4-formyl-3,5-dimethylpyrazolyl) instead of 3-formyl-6-phenyloxypyridine. ) Phenyl] -N, N-dimethylcarboxamide, and the same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical data.
TLC: Rf 0.62 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ7.65-7.52 (m, 4H), 4.33 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz, 1H), 3.96-3.72 (m, 2H), 3.64- 3.54 (m, 2H), 3.50-3.36 (m, 2H), 3.14 (s, 3H), 3.05 (s, 3H), 2.60-2.42 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.36-2.10 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H).

Examples 4 (1) to 4 (43)
The same operation as in Example 4 was performed using the corresponding aldehyde derivative instead of [4- (4-formyl-3,5-dimethylpyrazolyl) phenyl] -N, N-dimethylcarboxamide, and the following was performed. The compound of the present invention was obtained.

ＴＬＣ：Ｒｆ 0.56（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.96-3.74 (m, 2H), 3.66-3.36 (m, 8H), 2.58-2.40 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.34-2.12 (m, 2H), 2.06-1.26 (m, 11H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (1)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.56 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz) , 1H), 3.96-3.74 (m, 2H), 3.66-3.36 (m, 8H), 2.58-2.40 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.34-2.12 (m , 2H), 2.06-1.26 (m, 11H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.57（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.64 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.98-3.36 (m, 14H), 2.58-2.36 (m, 2H), 2.44 (s, 3H), 2.40 (s, 3H), 2.32-2.14 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (2)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.57 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.64 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz) , 1H), 3.98-3.36 (m, 14H), 2.58-2.36 (m, 2H), 2.44 (s, 3H), 2.40 (s, 3H), 2.32-2.14 (m, 2H), 1.90-1.24 (m , 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.09 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 4.48 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.56-3.36 (m, 4H), 3.16 (s, 3H), 2.48-2.30 (m, 2H), 2.28-2.06 (m, 2H), 1.90-1.24 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (3)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ8.09 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 4.48 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz) , 1H), 3.92-3.70 (m, 2H), 3.56-3.36 (m, 4H), 3.16 (s, 3H), 2.48-2.30 (m, 2H), 2.28-2.06 (m, 2H), 1.90-1.24 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H), 4.40 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.94-3.72 (m, 2H), 3.58-3.36 (m, 4H), 3.12 (s, 3H), 2.54-2.36 (m, 2H), 2.18-2.08 (m, 2H), 1.88-1.26 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (4)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.45 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H), 4.40 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.94-3.72 (m, 2H), 3.58-3.36 (m, 4H), 3.12 (s, 3H), 2.54-2.36 (m, 2H), 2.18-2.08 (m, 2H), 1.88-1.26 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz , 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.60（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 4.32 (s, 2H), 4.16-3.98 (m, 3H), 3.94-3.76 (m, 4H), 3.64-3.40 (m, 6H), 3.38-3.18 (m, 6H), 2.62-2.44 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.36-2.12 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (5)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) ethylaminosulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.60 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 4.32 (s, 2H), 4.16-3.98 (m, 3H), 3.94 -3.76 (m, 4H), 3.64-3.40 (m, 6H), 3.38-3.18 (m, 6H), 2.62-2.44 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.36 -2.12 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 9.0 Hz, 2H), 7.83 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz, 1H), 4.03-3.76 (m, 4H), 3.68-3.56 (m, 4H), 3.54-3.42 (m, 2H), 3.30-3.20 (m, 2H), 2.92 (s, 3H), 2.86-2.72 (m, 2H), 2.64-2.48 (m, 2H), 2.51 (s, 3H), 2.42 (s, 3H), 2.32-2.12 (m, 2H), 1.90-1.26 (m, 7H), 0.97 (t, J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (6)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.50 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 9.0 Hz, 2H), 7.83 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz) , 1H), 4.03-3.76 (m, 4H), 3.68-3.56 (m, 4H), 3.54-3.42 (m, 2H), 3.30-3.20 (m, 2H), 2.92 (s, 3H), 2.86-2.72 (m, 2H), 2.64-2.48 (m, 2H), 2.51 (s, 3H), 2.42 (s, 3H), 2.32-2.12 (m, 2H), 1.90-1.26 (m, 7H), 0.97 (t , J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.75 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 7.18 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.81 (s, 3H), 2.52-2.36 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.26 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (7)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.75 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 7.18 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.81 (s, 3H), 2.52-2.36 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.26 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz , 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.66 (s, 1H), 8.53-8.52 (m,1H), 7.88-7.78 (m, 2H), 7.77 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 4.41 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.66-3.40 (m, 4H), 2.66-2.48 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.26 (m, H), 0.96 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H)。 Example 4 (8)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane hydrochloride

TLC: Rf 0.48 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.66 (s, 1H), 8.53-8.52 (m, 1H), 7.88-7.78 (m, 2H), 7.77 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 4.41 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.66-3.40 (m, 4H), 2.66-2.48 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.26 (m, H), 0.96 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H), 0.94 ( d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz, 1H), 3.98-3.76 (m, 2H), 3.74 (t, J = 5.7 Hz, 2H), 3.68-3.58 (m, 2H), 3.54 (t, J = 5.7 Hz, 2H), 3.54-3.40 (m, 2H), 2.64-2.48 (m, 2H), 2.46 (s, 3H), 2.43 (s, 3H), 2.32-2.10 (m, 2H), 1.90-1.30 (m, 7H), 0.97 (t, J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (9)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J = 7.8, 4.5 Hz) , 1H), 3.98-3.76 (m, 2H), 3.74 (t, J = 5.7 Hz, 2H), 3.68-3.58 (m, 2H), 3.54 (t, J = 5.7 Hz, 2H), 3.54-3.40 ( m, 2H), 2.64-2.48 (m, 2H), 2.46 (s, 3H), 2.43 (s, 3H), 2.32-2.10 (m, 2H), 1.90-1.30 (m, 7H), 0.97 (t, J = 6.6 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.55（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.61 (d, J = 8.7 Hz, 2H), 7.49 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.36 (m, 14H), 2.58-2.38 (m, 2H), 2.28-2.08 (m, 2H), 1.88-1.28 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (10)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.55 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.61 (d, J = 8.7 Hz, 2H), 7.49 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.36 (m, 14H), 2.58-2.38 (m, 2H), 2.28-2.08 ( m, 2H), 1.88-1.28 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.66（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.00 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 4.34 (s, 2H), 4.04 (dd, J = 7.8, 4.5 Hz, 1H), 3.96-3.76 (m, 2H), 3.68-3.56 (m, 2H), 3.48-3.38 (m, 2H), 3.36-3.22 (m, 4H), 2.52-2.38 (m, 2H), 2.46 (s, 3H), 2.40 (s, 3H), 2.36-2.14 (m, 2H), 1.90-1.28 (m, 7H), 1.20-1.08 (m,6H), 0.97 (t, J = 7.5 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (11)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-diethylaminosulfonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.66 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.00 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 4.34 (s, 2H), 4.04 (dd, J = 7.8, 4.5 Hz) , 1H), 3.96-3.76 (m, 2H), 3.68-3.56 (m, 2H), 3.48-3.38 (m, 2H), 3.36-3.22 (m, 4H), 2.52-2.38 (m, 2H), 2.46 (s, 3H), 2.40 (s, 3H), 2.36-2.14 (m, 2H), 1.90-1.28 (m, 7H), 1.20-1.08 (m, 6H), 0.97 (t, J = 7.5 Hz, 3H ), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.88 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.90-3.76 (m, 2H), 3.70 (t, J = 6.0 Hz, 2H), 3 .56-3.36 (m, 4H), 3.50 (t, J = 6.0 Hz, 2H), 2.52-2.38 (m, 2H), 2.24-2.08 (m, 2H), 1.88-1.16 (m, 7H), 1.02-0.88 (m, 9H)。 Example 4 (12)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.88 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.07 (d, J) = 8.7 Hz, 2H), 4.36 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.90-3.76 (m, 2H), 3.70 (t, J = 6.0 Hz, 2H), 3 .56-3.36 (m, 4H), 3.50 (t, J = 6.0 Hz, 2H), 2.52-2.38 (m, 2H), 2.24-2.08 (m, 2H), 1.88-1.16 (m, 7H), 1.02 -0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.22（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.59 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.72 (m, 2H), 3.64-3.36 (m, 8H), 2.48-2.10 (m, 4H), 2.04-1.26 (m, 11H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (13)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.22 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.59 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.72 (m, 2H), 3.64-3.36 (m, 8H), 2.48-2.10 ( m, 4H), 2.04-1.26 (m, 11H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.44 (m, 2H), 3.06 (m, 1H), 2.68-2.50 (m, 2H), 2.47 (s, 3H), 2.41 (s, 3H), 2.38-2.08 (m, 2H), 1.82-1.06 (m, 25H), 1.02-0.86 (m, 5H)。 Example 4 (14)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz) , 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.44 (m, 2H), 3.06 (m, 1H), 2.68-2.50 (m, 2H), 2.47 (s , 3H), 2.41 (s, 3H), 2.38-2.08 (m, 2H), 1.82-1.06 (m, 25H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz, 1H), 3.94-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.46 (m, 2H), 3.39 (t, J = 6.0 Hz, 2H), 3.26 (s, 3H), 2 .98 (t, J = 6.9 Hz, 2H), 2.72-2.58 (m, 2H), 2.48 (s, 3H), 2.42 (s, 3H), 2.26-2.10 (m, 2H), 1.90-1.28 (m, 9H), 0.98-0.90 (m, 9H)。 Example 4 (15)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz) , 1H), 3.94-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.46 (m, 2H), 3.39 (t, J = 6.0 Hz, 2H), 3.26 (s, 3H), 2.98 (t, J = 6.9 Hz, 2H), 2.72-2.58 (m, 2H), 2.48 (s, 3H), 2.42 (s, 3H), 2.26-2.10 (m, 2H), 1.90-1.28 ( m, 9H), 0.98-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.13（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.88 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.47 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz, 1H), 3.96-3.74 (m, 2H), 3.56-3.36 (m, 4H), 2.83 (s, 3H), 2.52-2.34 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.26 (m, 7H), 0.95 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (16)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.13 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.88 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.47 (s, 2H), 4.02 (dd, J = 7.8, 4.8 Hz) , 1H), 3.96-3.74 (m, 2H), 3.56-3.36 (m, 4H), 2.83 (s, 3H), 2.52-2.34 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.26 (m, 7H), 0.95 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.58（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.26 (s, 2H), 4.10 (t, J = 7.2 Hz, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.68 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.44 (s, 3H), 2.38 (s, 3H), 2.30-2.10 (m, 2H), 1.92-1.24 (m, 9H), 0.96 (t, J = 7.2 Hz, 6H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H)。 Example 4 (17)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

TLC: Rf 0.58 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 4.26 (s, 2H), 4.10 (t, J = 7.2 Hz, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.68 (m, 2H) , 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.44 (s, 3H), 2.38 (s, 3H), 2.30-2.10 (m, 2H), 1.92-1.24 (m, 9H) , 0.96 (t, J = 7.2 Hz, 6H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.58（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.34-4.24 (m, 4H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.68 (m, 2H), 3.62-3.46 (m, 4H), 2.74-2.60 (m, 2H), 2.53 (s, 3H), 2.50 (s, 3H), 2.24-2.06 (m, 2H), 1.88-1.26 (m, 10H), 1.02-0.86 (m, 9H)。 Example 4 (18)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

TLC: Rf 0.58 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.34-4.24 (m, 4H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.68 (m, 2H), 3.62-3.46 (m, 4H), 2.74-2.60 (m, 2H), 2.53 (s, 3H), 2.50 (s, 3H), 2.24-2.06 (m, 2H), 1.88-1.26 (m, 10H), 1.02-0.86 (m, 9H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ5.00-4.82 (m, 1H), 4.31 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.62-3.46 (m, 4H), 2.78-2.58 (m, 2H), 2.55 (s, 3H), 2.53 (s, 3H), 2.32-2.04 (m, 4H), 2.04-1.26 (m, 13H), 0.98-0. 84 (m, 9H)。 Example 4 (19)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ5.00-4.82 (m, 1H), 4.31 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.62- 3.46 (m, 4H), 2.78-2.58 (m, 2H), 2.55 (s, 3H), 2.53 (s, 3H), 2.32-2.04 (m, 4H), 2.04-1.26 (m, 13H), 0.98- 0.84 (m, 9H).

ＴＬＣ：Ｒｆ 0.15（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.23 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.68 (m, 2H), 3.58-3.36 (m, 4H), 2.56 (s, 3H), 2.56-2.38 (m, 2H), 2.32 (s, 3H), 2.32-2.10 (m, 2H), 1.88-1.26 (m, 7H), 1.67 (s, 9H), 0.96 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H)。 Example 4 (20)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.15 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.23 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.68 (m, 2H), 3.58-3.36 (m, 4H), 2.56 ( s, 3H), 2.56-2.38 (m, 2H), 2.32 (s, 3H), 2.32-2.10 (m, 2H), 1.88-1.26 (m, 7H), 1.67 (s, 9H), 0.96 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.17（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.42-7.26 (m, 5H), 5.15 (s, 2H), 4.48-4.22 (m, 3H), 4.23 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.58-3.36 (m, 4H), 3.12-2.90 (m, 2H), 2.50-1.28 (m, 15H), 2.42 (s, 3H), 2.30 (s, 3H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (21)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazole-4- Ilmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.17 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.42-7.26 (m, 5H), 5.15 (s, 2H), 4.48-4.22 (m, 3H), 4.23 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.58-3.36 (m, 4H), 3.12-2.90 (m, 2H), 2.50-1.28 (m, 15H), 2.42 (s, 3H), 2.30 ( s, 3H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.00 (dd, J = 7.5, 4.8 Hz, 1H), 3.91-3.72 (m, 2H), 3.76 (s, 3H), 3.53-3.35 (m, 4H), 2.50-2.35 (m, 2H), 2.26-2.08 (m, 2H), 1.87-1.28 (m, 7H), 0.94 (t, J = 7.5 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H)。 Example 4 (22)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.00 (dd, J = 7.5, 4.8 Hz, 1H), 3.91-3.72 (m, 2H), 3.76 (s, 3H) , 3.53-3.35 (m, 4H), 2.50-2.35 (m, 2H), 2.26-2.08 (m, 2H), 1.87-1.28 (m, 7H), 0.94 (t, J = 7.5 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.92 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 4.43 (s, 2H), 4.00 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.75 (m, 2H), 3.53-3.35 (m, 8H), 3.34 (s, 3H), 2.50-2.35 (m, 2H), 2.27-2.10 (m, 2H), 1.92-1.28 (m, 9H), 0.94 (t, J = 7.2 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H)。 Example 4 (23)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.48 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.92 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 4.43 (s, 2H), 4.00 (dd, J = 7.8, 4.5 Hz) , 1H), 3.92-3.75 (m, 2H), 3.53-3.35 (m, 8H), 3.34 (s, 3H), 2.50-2.35 (m, 2H), 2.27-2.10 (m, 2H), 1.92-1.28 (m, 9H), 0.94 (t, J = 7.2 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.29（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.19 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 4.28 (s, 2H), 4.03 (m, 1H), 3.94 (s, 3H), 3.95-3.30 (m, 6H), 2.50-2.15 (m, 4H), 2.44 (s, 3H), 2.39 (s, 3H), 1.90-1.30 (m, 7H),0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H) 0.94 (d, J = 6.6 Hz, 3H)。 Example 4 (24)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1, 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.29 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.19 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 4.28 (s, 2H), 4.03 (m, 1H), 3.94 (s , 3H), 3.95-3.30 (m, 6H), 2.50-2.15 (m, 4H), 2.44 (s, 3H), 2.39 (s, 3H), 1.90-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H) 0.94 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.31（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.37 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (m, 1H), 4.00-3.30 (m, 6H), 3.86 (s, 3H), 2.65-2.15 (m, 4H), 2.39 (s, 3H), 2.34 (s, 3H), 1.90-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H) 0.94 (d, J = 6.6 Hz, 3H)。 Example 4 (25)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.31 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.37 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (m, 1H), 4.00-3.30 (m, 6H), 3.86 (s, 3H), 2.65-2.15 (m, 4H), 2.39 (s, 3H), 2.34 (s, 3H), 1.90-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H) 0.94 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.18（酢酸エチル：メタノール＝３：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.10-4.00 (m, 3H), 4.00-3.00 (m, 16H), 2.70-2.10 (m, 4H), 2.48 (s, 3H), 2.40 (s, 3H), 2.10-1.90 (m, 2H), 1.90-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H)。 Example 4 (26)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) propylaminosulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.18 (ethyl acetate: methanol = 3: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.10-4.00 (m, 3H), 4.00 -3.00 (m, 16H), 2.70-2.10 (m, 4H), 2.48 (s, 3H), 2.40 (s, 3H), 2.10-1.90 (m, 2H), 1.90-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H).

ＴＬＣ：Ｒｆ 0.55（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.71-7.59 (m, 4H), 4.41 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.83-3.72 (m, 2H), 3.60 (t, J = 6.9 Hz, 2H), 3.55-3.32 (m, 4H), 3.45 (t, J = 6.9 Hz, 2H), 2.57-2.37 (m, 2H), 2.27-2.08 (m, 2H), 2.05-1.44 (m, 9H), 1.44-1.27 (m, 2H), 0.99-0.90 (m, 9H)。 Example 4 (27)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.55 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.71-7.59 (m, 4H), 4.41 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.83-3.72 (m, 2H), 3.60 ( t, J = 6.9 Hz, 2H), 3.55-3.32 (m, 4H), 3.45 (t, J = 6.9 Hz, 2H), 2.57-2.37 (m, 2H), 2.27-2.08 (m, 2H), 2.05 -1.44 (m, 9H), 1.44-1.27 (m, 2H), 0.99-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.60（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.69 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz, 1H), 3.93-3.72 (m, 4H), 3.55-3.30 (m, 6H), 2.57-2.39 (m, 2H), 2.26-2.07 (m, 2H), 1.90-1.44 (m, 11H), 1.44-1.26 (m, 2H), 0.98-0.90 (m, 9H)。 Example 4 (28)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.60 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.69 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz) , 1H), 3.93-3.72 (m, 4H), 3.55-3.30 (m, 6H), 2.57-2.39 (m, 2H), 2.26-2.07 (m, 2H), 1.90-1.44 (m, 11H), 1.44 -1.26 (m, 2H), 0.98-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.59（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.69 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.93-3.55 (m, 8H), 3.55-3.34 (m, 6H), 2.55-2.36 (m, 2H), 2.27-2.08 (m, 2H), 1.88-1.44 (m, 5H), 1.44-1.28 (m, 2H), 0.98-0.90 (m, 9H)。 Example 4 (29)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.59 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.69 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz) , 1H), 3.93-3.55 (m, 8H), 3.55-3.34 (m, 6H), 2.55-2.36 (m, 2H), 2.27-2.08 (m, 2H), 1.88-1.44 (m, 5H), 1.44 -1.28 (m, 2H), 0.98-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.80 (d, J = 6.0 Hz, 1H), 8.58 (m, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.98 (m, 1H), 7.70 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 4.39 (s, 2H), 4.05-3.95 (m, 3H), 3.94-3.69 (m, 2H), 3.60-3.37 (m, 6H), 3.08 (s, 3H), 2.70-2.43 (m, 2H), 2.26-2.05 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.26 (m, 2H), 0.99-0.90 (m, 9H)。 Example 4 (30)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) aminocarbonyl) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.80 (d, J = 6.0 Hz, 1H), 8.58 (m, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.98 (m, 1H), 7.70 (d , J = 7.8 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 4.39 (s, 2H), 4.05-3.95 (m, 3H), 3.94-3.69 (m, 2H), 3.60-3.37 ( m, 6H), 3.08 (s, 3H), 2.70-2.43 (m, 2H), 2.26-2.05 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.26 (m, 2H), 0.99- 0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.33（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.92 (d, J = 8.1 Hz, 2H), 7.69 (d, J = 8.1 Hz, 2H), 4.43 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz, 1H), 3.96-3.70 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.28-2.06 (m, 2H), 2.04-1.12 (m, 18H), 0.95 (t, J = 6.9 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H), 0.93 (d, J = 6.3 Hz, 3H)。 Example 4 (31)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.33 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.92 (d, J = 8.1 Hz, 2H), 7.69 (d, J = 8.1 Hz, 2H), 4.43 (s, 2H), 4.01 (dd, J = 7.5, 4.5 Hz) , 1H), 3.96-3.70 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.28-2.06 (m, 2H), 2.04-1.12 (m, 18H), 0.95 (t, J = 6.9 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H), 0.93 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.44（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.91 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H), 4.49 (s, 2H), 4.02 (dd, J = 7.5, 4.8 Hz, 1H), 3.96-3.76 (m, 2H), 3.56-3.38 (m, 4H), 2.72 (s, 6H), 2.60-2.40 (m, 2H), 2.28-2.06 (m, 2H), 1.90-1.28 (m, 7H), 0.95 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (32)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9-triazaspiro [5 .5] Undecane hydrochloride

TLC: Rf 0.44 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.91 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H), 4.49 (s, 2H), 4.02 (dd, J = 7.5, 4.8 Hz) , 1H), 3.96-3.76 (m, 2H), 3.56-3.38 (m, 4H), 2.72 (s, 6H), 2.60-2.40 (m, 2H), 2.28-2.06 (m, 2H), 1.90-1.28 (m, 7H), 0.95 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90 (s, 3H), 3.88-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.30-2.08 (m, 2H), 1.90-1.28 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 4 (33)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

TLC: Rf 0.50 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.02 (dd, J = 7.5, 4.5 Hz, 1H), 3.90 (s, 3H), 3.88-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.30-2.08 (m, 2H), 1.90-1.28 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.95 (d, J = 6.3 Hz , 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.15（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.56 (m, 1H), 4.20 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.86-3.42 (m, 8H), 3.30-3.20 (m, 2H), 2.93 (s, 3H), 2.64-2.48 (m, 2H), 2.44-2.28 (m, 2H), 2.44 (s, 3H), 2.31 (s, 3H), 2.22-2.06 (m, 4H), 1.86-1.28 (m, 7H), 0.98-0.88 (m, 9H)。 Example 4 (34)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-Triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.15 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 4.56 (m, 1H), 4.20 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.86-3.42 (m, 8H), 3.30-3.20 ( m, 2H), 2.93 (s, 3H), 2.64-2.48 (m, 2H), 2.44-2.28 (m, 2H), 2.44 (s, 3H), 2.31 (s, 3H), 2.22-2.06 (m, 4H), 1.86-1.28 (m, 7H), 0.98-0.88 (m, 9H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.46 (m, 1H), 4.25 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.68 (m, 4H), 3.60-3.42 (m, 4H), 3.04-2.90 (m, 2H), 2.89 (s, 3H), 2.62-2.46 (m, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.24-1.98 (m, 6H), 1.90-1.28 (m, 7H), 0.98-0.90 (m, 9H)。 Example 4 (35)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ4.46 (m, 1H), 4.25 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.68 (m, 4H), 3.60-3.42 ( m, 4H), 3.04-2.90 (m, 2H), 2.89 (s, 3H), 2.62-2.46 (m, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.24-1.98 (m, 6H), 1.90-1.28 (m, 7H), 0.98-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.22（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.84-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.55-3.44 (m, 2H), 3.27-3.18 (m, 2H), 3.02 (t, J = 6.3 Hz, 2 H), 2.89 (s, 6H), 2.70-2.52 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.28-2.11 (m, 2H), 2.00-1.28 (m, 9H), 1.00-0.90 (m, 9H)。 Example 4 (36)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) propylamino Sulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.22 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz) , 1H), 3.84-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.55-3.44 (m, 2H), 3.27-3.18 (m, 2H), 3.02 (t, J = 6.3 Hz, 2 H), 2.89 (s, 6H), 2.70-2.52 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.28-2.11 (m, 2H), 2.00-1.28 (m, 9H) , 1.00-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.61（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.68-7.60 (m, 4H), 7.21 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.00 (dd, J = 7.8, 4.8 Hz, 1H), 3.89-3.77 (m, 2H), 3.54-3.40 (m, 4H), 3.28 (s, 6H), 2.62-2.44 (m, 2H), 2.26-2.07 (m, 2H), 1.90-1.26 (m, 7H), 1.00-0.90 (m, 9H)。 Example 4 (37)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.61 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.68-7.60 (m, 4H), 7.21 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 4.35 (s, 2H), 4.00 (dd, J = 7.8, 4.8 Hz, 1H), 3.89-3.77 (m, 2H), 3.54-3.40 (m, 4H), 3.28 (s, 6H), 2.62-2.44 (m, 2H), 2.26-2.07 (m, 2H), 1.90-1.26 (m, 7H), 1.00-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.34（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.95-3.73 (m, 2H), 3.66-3.54 (m, 2H), 3.54-3.43 (m, 2H), 3.42 (s, 4H), 3.01 (s, 6H), 2.85 (s, 3H), 2.68-2.52 (m, 2H), 2.50 (s, 3H), 2.41 (s, 3H), 2.29-2.10 (m, 2H), 1.90-1.28 (m, 7H), 1.00-0.90 (m, 9H)。 Example 4 (38)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′ , N'-Dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane / 3 hydrochloride

TLC: Rf 0.34 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz) , 1H), 3.95-3.73 (m, 2H), 3.66-3.54 (m, 2H), 3.54-3.43 (m, 2H), 3.42 (s, 4H), 3.01 (s, 6H), 2.85 (s, 3H ), 2.68-2.52 (m, 2H), 2.50 (s, 3H), 2.41 (s, 3H), 2.29-2.10 (m, 2H), 1.90-1.28 (m, 7H), 1.00-0.90 (m, 9H) ).

ＴＬＣ：Ｒｆ 0.29（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ7.62 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.18-7.10 (m, 4H), 4.35 (s, 2H), 4.30 (s, 2H), 4.00 (dd, J = 7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.54-3.38 (m, 4H), 2.86 (s, 6H), 2.59-2.42 (m, 2H), 2.26-2.07 (m, 2H), 1.88-1.25 (m, 7H), 1.02-0.89 (m, 9H)。 Example 4 (39)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.29 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 7.62 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.18-7.10 (m, 4H), 4.35 (s, 2H), 4.30 (s, 2H), 4.00 (dd, J = 7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.54-3.38 (m, 4H), 2.86 (s, 6H), 2.59-2.42 (m , 2H), 2.26-2.07 (m, 2H), 1.88-1.25 (m, 7H), 1.02-0.89 (m, 9H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.84-3.64 (m, 2H), 3.52-3.35 (m, 4H), 2.48-2.3 2 (m, 2H), 2.27-2.10 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.26 (m, 2H), 0.99-0.90 (m, 9H)。 Example 4 (40)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane hydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.84-3.64 (m, 2H), 3.52-3.35 (m, 4H), 2.48-2.3 2 (m, 2H), 2.27-2.10 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.26 (m, 2H), 0.99-0.90 (m, 9H).

ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.34 (s, 2H), 4.03 (dd, J = 7.8, 4.8 Hz, 1H), 3.96-3.74 (m, 2H), 3.70-3.42 (m, 4H), 2.96 (s, 3H), 2.74-2.54 (m, 2H), 2.47 (s, 3H), 2.46 (s, 3H), 2.30-2.10 (m, 2H), 1.92-1.28 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H)。 Example 4 (41)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.34 (s, 2H), 4.03 (dd, J = 7.8, 4.8 Hz) , 1H), 3.96-3.74 (m, 2H), 3.70-3.42 (m, 4H), 2.96 (s, 3H), 2.74-2.54 (m, 2H), 2.47 (s, 3H), 2.46 (s, 3H ), 2.30-2.10 (m, 2H), 1.92-1.28 (m, 7H), 0.96 (t, J = 6.9 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H).

ＮＭＲ（CDCl₃）：δ7.78 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 6.70 (t, J = 4.8 Hz, 1H), 6.40 (brs, 1H), 4.26 (d, J = 4.8 Hz, 2H), 3.96 (m, 1H), 3.81 (s, 3H), 3.62 (s, 2H), 3.50-3.28 (m, 2H), 3.00-2.48 (m, 8H), 2.26-1.20 (m, 7H), 0.99-0.94 (m, 9H)。 Example 4 (42)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5 .5] Undecane

NMR (CDCl ₃ ): δ 7.78 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 6.70 (t, J = 4.8 Hz, 1H), 6.40 (brs, 1H) , 4.26 (d, J = 4.8 Hz, 2H), 3.96 (m, 1H), 3.81 (s, 3H), 3.62 (s, 2H), 3.50-3.28 (m, 2H), 3.00-2.48 (m, 8H ), 2.26-1.20 (m, 7H), 0.99-0.94 (m, 9H).

ＮＭＲ（CDCl₃）：δ7.56-7.32 (m, 5H), 6.54 (m, 1H), 6.38 (brs, 1H), 5.96 (m, 1H), 4.00 (m, 1H), 3.76-2.90 (m, 8H), 2.38 (s, 3H), 2.34 (s, 3H), 2.14-1.22 (m, 11H), 1.00-0.86 (m, 9H)。 Example 4 (43)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) -2E-propenyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

NMR (CDCl ₃ ): δ7.56-7.32 (m, 5H), 6.54 (m, 1H), 6.38 (brs, 1H), 5.96 (m, 1H), 4.00 (m, 1H), 3.76-2.90 (m , 8H), 2.38 (s, 3H), 2.34 (s, 3H), 2.14-1.22 (m, 11H), 1.00-0.86 (m, 9H).

実施例４（４２）で製造した化合物（１０６ｍｇ）のメタノール（３ｍｌ）溶液に、５Ｎ水酸化ナトリウム水溶液（0.1ｍｌ）を加えた。反応混合物を室温で３時間撹拌した。反応混合物を濃縮し、残渣をジオキサンに溶解させた。この溶液に、４Ｎ塩化水素酢酸エチル溶液を加えた。反応混合物を濃縮し、得られた残渣にジオキサンを加え、ろ過した。ろ液を濃縮し、得られた残渣をエーテル洗浄し、乾燥し、以下の物性値を有する本発明化合物（６２ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.28（ブタノール：酢酸：水＝４：２：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 8.7 Hz, 2H), 4.44 (s, 2H), 4.11 (s, 2H), 4.02 (dd, J = 7.5, 4.8 Hz, 1H), 3.94-3.74 (m, 2H), 3.56-3.36 (m, 4H), 2.48-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.88-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 5
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane hydrochloride

To a solution of the compound (106 mg) produced in Example 4 (42) in methanol (3 ml) was added a 5N aqueous sodium hydroxide solution (0.1 ml). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the residue was dissolved in dioxane. To this solution was added a 4N solution of hydrogen chloride in ethyl acetate. The reaction mixture was concentrated, dioxane was added to the obtained residue, and the mixture was filtered. The filtrate was concentrated, and the obtained residue was washed with ether and dried to give the compound of the present invention (62 mg) having the following physical data.
TLC: Rf 0.28 (butanol: acetic acid: water = 4: 2: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 8.7 Hz, 2H), 4.44 (s, 2H), 4.11 (s, 2H), 4.02 (dd , J = 7.5, 4.8 Hz, 1H), 3.94-3.74 (m, 2H), 3.56-3.36 (m, 4H), 2.48-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.88-1.30 (m, 7H), 0.96 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

実施例４（４３）で製造した化合物（８５ｍｇ）をメタノール（１０ｍｌ）溶液に、５％パラジウム炭素（１０ｍｇ）を加えた。反応混合物を水素ガス雰囲気下、室温で２２時間撹拌した。反応混合物をセライト（商品名）を用いて、ろ過し、ろ液を濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル：メタノール＝１５：１）によって精製した。得られた化合物のメタノール溶液に、４Ｎ塩化水素酢酸エチル溶液を加えた。反応混合物を濃縮し、得られた残渣をエーテル洗浄し、乾燥し、以下の物性値を有する本発明化合物（２３ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.18（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.70-7.50 (m, 5H), 4.03 (dd J = 7.2, 4.2 Hz, 1H), 3.86-3.68 (m, 2H), 3.66-3.40 (m, 4H), 3.30-3.16 (m, 2H), 2.74-2.48 (m, 4H), 2.46 (s, 3H), 2.35 (s, 3H), 2.28-1.98 (m, 4H), 1.90-1.24 (m, 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H)。 Example 6
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) propyl) -1,4 , 9-Triazaspiro [5.5] undecane dihydrochloride

5% palladium carbon (10 mg) was added to a solution of the compound (85 mg) produced in Example 4 (43) in methanol (10 ml). The reaction mixture was stirred at room temperature under a hydrogen gas atmosphere for 22 hours. The reaction mixture was filtered using Celite (trade name), and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate: methanol = 15: 1). To a methanol solution of the obtained compound was added a 4N solution of hydrogen chloride in ethyl acetate. The reaction mixture was concentrated, and the obtained residue was washed with ether and dried to give the compound of the present invention (23 mg) having the following physical data.
TLC: Rf 0.18 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.70-7.50 (m, 5H), 4.03 (dd J = 7.2, 4.2 Hz, 1H), 3.86-3.68 (m, 2H), 3.66-3.40 (m, 4H), 3.30 -3.16 (m, 2H), 2.74-2.48 (m, 4H), 2.46 (s, 3H), 2.35 (s, 3H), 2.28-1.98 (m, 4H), 1.90-1.24 (m, 7H), 0.97 (t, J = 7.2 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（２）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、［４−（４−ホルミル−３，５−ジメチルピラゾリル）フェニル］−Ｎ，Ｎ−ジメチルカルボキサミドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.59（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.05 (dd, J = 7.8, 4.5 Hz, 1H), 3.96-3.78 (m, 2H), 3.66-3.58 (m, 2H), 3.46-3.34 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.52-2.38 (m, 2H), 2.42 (s, 3H), 2.39 (s, 3H), 2.32-2.14 (m, 2H), 1.82-1.16 (m, 15H), 1.02-0.88 (m, 5H)。 Example 7
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-Triazaspiro [5.5] undecane dihydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (2) was replaced with [4- (4-formyl-3,5-dimethylpyrazolyl) instead of 3-formyl-6-phenyloxypyridine. ) Phenyl] -N, N-dimethylcarboxamide, and the same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical data.
TLC: Rf 0.59 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.05 (dd, J = 7.8, 4.5 Hz) , 1H), 3.96-3.78 (m, 2H), 3.66-3.58 (m, 2H), 3.46-3.34 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.52-2.38 (m , 2H), 2.42 (s, 3H), 2.39 (s, 3H), 2.32-2.14 (m, 2H), 1.82-1.16 (m, 15H), 1.02-0.88 (m, 5H).

Examples 7 (1) to 7 (41)
The same operation as in Example 7 was performed using the corresponding aldehyde derivative instead of [4- (4-formyl-3,5-dimethylpyrazolyl) phenyl] -N, N-dimethylcarboxamide. The compound of the present invention was obtained.

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.72 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.98-3.78 (m, 2H), 3.64-3.56 (m, 4H), 3.56-3.44 (m, 2H), 3.44-3.32 (m, 2H), 2.50-2.10 (m, 4H), 2.4 2 (s, 3H), 2.39 (s, 3H), 2.10-1.88 (m, 4H), 1.88-1.10 (m, 15H), 1.10-0.90 (m, 5H)。 Example 7 (1)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.72 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz) , 1H), 3.98-3.78 (m, 2H), 3.64-3.56 (m, 4H), 3.56-3.44 (m, 2H), 3.44-3.32 (m, 2H), 2.50-2.10 (m, 4H), 2.4 2 (s, 3H), 2.39 (s, 3H), 2.10-1.88 (m, 4H), 1.88-1.10 (m, 15H), 1.10-0.90 (m, 5H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.65-7.56 (m, 4H), 4.32 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.96-3.30 (m, 14H), 2.54-2.32 (m, 2H), 2.43 (s, 3H), 2.39 (s, 3H), 2.32-2.12 (m, 2H), 1.84-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (2)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.65-7.56 (m, 4H), 4.32 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.96-3.30 (m, 14H), 2.54- 2.32 (m, 2H), 2.43 (s, 3H), 2.39 (s, 3H), 2.32-2.12 (m, 2H), 1.84-1.10 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.15（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.2, 5.1 Hz, 1H), 3.94-3.76 (m, 2H), 3.79 (t, J = 6.0 Hz, 2H), 3.66-3.54 (m, 2H), 3.54-3.36 (m, 2H), 3.41 (t, J = 6. 0 Hz, 2H), 3.00 (s, 6H), 2.66-2.48 (m, 2H), 2.46 (s, 3H), 2.41 (s, 3H), 2.28-2.10 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (3)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) ethylaminocarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.15 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.2, 5.1 Hz) , 1H), 3.94-3.76 (m, 2H), 3.79 (t, J = 6.0 Hz, 2H), 3.66-3.54 (m, 2H), 3.54-3.36 (m, 2H), 3.41 (t, J = 6 0 Hz, 2H), 3.00 (s, 6H), 2.66-2.48 (m, 2H), 2.46 (s, 3H), 2.41 (s, 3H), 2.28-2.10 (m, 2H), 1.82-1.10 ( m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.60（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.59 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.22-7.09 (m, 4H), 4.36 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.88-3.34 (m, 14H), 2.52-2.34 (m, 2H), 2.28-2.08 (m, 2H), 1.81-1.10 (m, 15H), 1. 04-0.84 (m, 5H)。 Example 7 (4)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.60 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.59 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.22-7.09 (m, 4H), 4.36 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.88-3.34 (m, 14H), 2.52-2.34 (m, 2H), 2.28-2.08 (m, 2H), 1.81-1.10 (m, 15H), 1 04-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.57（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.08 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 4.50 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.94-3.76 (m, 2H), 3.52-3.36 (m, 4H), 3.15 (s, 3H), 2.56-2.38 (m, 2H), 2.26-2.08 (m, 2H), 1.80-1.1 0 (m, 15H), 1. 02-0.86 (m, 5H)。 Example 7 (5)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.57 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.08 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 4.50 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz) , 1H), 3.94-3.76 (m, 2H), 3.52-3.36 (m, 4H), 3.15 (s, 3H), 2.56-2.38 (m, 2H), 2.26-2.08 (m, 2H), 1.80-1.1 0 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.57（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 9.0 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.25-7.18 (m, 4H), 4.39 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.76 (m, 2H), 3.58-3.34 (m, 4H), 3.12 (s, 3H), 2.50-2.36 (m, 2H), 2.30-2.1 0 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.88 (m, 5H)。 Example 7 (6)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.57 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 9.0 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.25-7.18 (m, 4H), 4.39 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.76 (m, 2H), 3.58-3.34 (m, 4H), 3.12 (s, 3H), 2.50-2.36 (m, 2H), 2.30-2.1 0 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.43（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.06 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.12-4.01 (m, 3H), 3.92-3.76 (m, 4H), 3.65-3.40 (m, 6H), 3.40-3.16 (m, 6H), 2.64-2.44 (m, 2H), 2.48 (s, 3H), 2.41 (s, 3H), 2.28-2. 12 (m, 2H), 1.84-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (7)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) ethylaminosulfonyl) phenyl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.43 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.06 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.12-4.01 (m, 3H), 3.92 -3.76 (m, 4H), 3.65-3.40 (m, 6H), 3.40-3.16 (m, 6H), 2.64-2.44 (m, 2H), 2.48 (s, 3H), 2.41 (s, 3H), 2.28 -2. 12 (m, 2H), 1.84-1.10 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.43（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.08-3.95 (m, 3H), 3.95-3.74 (m, 2H), 3.68-3.46 (m, 6H), 3.28-3.20 (m, 2H), 2.91 (s, 3H), 2.88-2.72 (m, 2H), 2.70-2.52 (m, 2H), 2. 51 (s, 3H), 2.42 (s, 3H), 2.26-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (8)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) phenyl) pyrazole-4- Ilmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.43 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.08-3.95 (m, 3H), 3.95 -3.74 (m, 2H), 3.68-3.46 (m, 6H), 3.28-3.20 (m, 2H), 2.91 (s, 3H), 2.88-2.72 (m, 2H), 2.70-2.52 (m, 2H) , 2.51 (s, 3H), 2.42 (s, 3H), 2.26-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.74 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.25-7.14 (m, 4H), 4.37 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.54-3.36 (m, 4H), 2.80 (s, 3H), 2.52-2.36 (m, 2H), 2.26-2.1 0 (m, 2H), 1.80-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (9)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.74 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.25-7.14 (m, 4H), 4.37 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.54-3.36 (m, 4H), 2.80 (s, 3H), 2.52-2.36 (m, 2H), 2.26-2.1 0 (m, 2H), 1.80-1.10 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.05 (dd, J = 7.5, 4.2 Hz, 1H), 3.92-3.68 (m, 4H), 3.66-3.42 (m, 6H), 2.70-2.50 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.28-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.84 (m, 5H)。 Example 7 (10)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.05 (dd, J = 7.5, 4.2 Hz) , 1H), 3.92-3.68 (m, 4H), 3.66-3.42 (m, 6H), 2.70-2.50 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.28-2.08 (m , 2H), 1.82-1.10 (m, 15H), 1.02-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.89 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.70 (t, J = 6.0 Hz, 2H), 3 .58-3.46 (m, 2H), 3.50 (t, J = 6.0 Hz, 2H), 3.42-3.34 (m, 2H), 2.44-2.30 (m, 2H), 2.30-2.08 (m, 2H), 1.82-1.12 (m, 15H), 1.02-0.84 (m, 5H)。 Example 7 (11)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.89 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.08 (d, J) = 9.0 Hz, 2H), 4.37 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.70 (t, J = 6.0 Hz, 2H), 3 .58-3.46 (m, 2H), 3.50 (t, J = 6.0 Hz, 2H), 3.42-3.34 (m, 2H), 2.44-2.30 (m, 2H), 2.30-2.08 (m, 2H), 1.82 -1.12 (m, 15H), 1.02-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.25（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.59 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.05 (dd, J = 7.5, 4.8 Hz, 1H), 3.90-3.74 (m, 2H), 3.62-3.36 (m, 8H), 2.48-2.08 (m, 4H), 2.04-1.08 (m, 19H), 0.96 (t, J = 7.2 Hz, 3H), 1.04-0.84 (m, 2H)。 Example 7 (12)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.25 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.59 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.05 (dd, J = 7.5, 4.8 Hz, 1H), 3.90-3.74 (m, 2H), 3.62-3.36 (m, 8H), 2.48-2.08 ( m, 4H), 2.04-1.08 (m, 19H), 0.96 (t, J = 7.2 Hz, 3H), 1.04-0.84 (m, 2H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.44 (m, 2H), 3.06 (m, 1H), 2.68-2.50 (m, 2H), 2.47 (s, 3H), 2.41 (s, 3H), 2.38-2.08 (m, 2H), 1.82-1.06 (m, 25H), 1.02-0.86 (m, 5H)。 Example 7 (13)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz) , 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.44 (m, 2H), 3.06 (m, 1H), 2.68-2.50 (m, 2H), 2.47 (s , 3H), 2.41 (s, 3H), 2.38-2.08 (m, 2H), 1.82-1.06 (m, 25H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.46 (m, 4H), 3.39 (t, J = 6.0 Hz, 2H), 3.26 (s, 3H), 2 .98 (t, J = 6.9 Hz, 2H), 2.72-2.56 (m, 2H), 2.48 (s, 3H), 2.43 (s, 3H), 2.26-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (14)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J = 7.8, 4.8 Hz) , 1H), 3.92-3.72 (m, 2H), 3.68-3.58 (m, 2H), 3.56-3.46 (m, 4H), 3.39 (t, J = 6.0 Hz, 2H), 3.26 (s, 3H), 2.98 (t, J = 6.9 Hz, 2H), 2.72-2.56 (m, 2H), 2.48 (s, 3H), 2.43 (s, 3H), 2.26-2.08 (m, 2H), 1.82-1.10 ( m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.15（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.85 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.47 (s, 2H), 4.05 (dd, J = 7.2, 4.8 Hz, 1H), 3.94-3.76 (m, 2H), 3.58-3.36 (m, 4H), 2.83 (s, 3H), 2.54-2.34 (m, 2H), 2.18-2.06 (m, 2H), 1.82-1.10 (m, 15H), 0.96 (t, J = 7.5 Hz, 3H), 1.06-0.86 (m, 2H)。 Example 7 (15)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.15 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.85 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 4.47 (s, 2H), 4.05 (dd, J = 7.2, 4.8 Hz) , 1H), 3.94-3.76 (m, 2H), 3.58-3.36 (m, 4H), 2.83 (s, 3H), 2.54-2.34 (m, 2H), 2.18-2.06 (m, 2H), 1.82-1.10 (m, 15H), 0.96 (t, J = 7.5 Hz, 3H), 1.06-0.86 (m, 2H).

ＴＬＣ：Ｒｆ 0.61（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.28 (s, 2H), 4.13 (t, J = 7.2 Hz, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.60-3.38 (m, 4H), 2.62-2.32 (m, 2H), 2.46 (s, 3H), 2.42 (s, 3H), 2.28-2.08 (m, 2H), 1.94-1.08 (m, 17H), 0.96 (t, J = 7.2 Hz, 6H), 1.06-0.86 (m, 2H)。 Example 7 (16)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] Undecane dihydrochloride

TLC: Rf 0.61 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.28 (s, 2H), 4.13 (t, J = 7.2 Hz, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H) , 3.60-3.38 (m, 4H), 2.62-2.32 (m, 2H), 2.46 (s, 3H), 2.42 (s, 3H), 2.28-2.08 (m, 2H), 1.94-1.08 (m, 17H) , 0.96 (t, J = 7.2 Hz, 6H), 1.06-0.86 (m, 2H).

ＴＬＣ：Ｒｆ 0.51（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.34-4.20 (m, 4H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.88-3.70 (m, 2H), 3.62-3.46 (m, 4H), 2.72-2.54 (m, 2H), 2.52 (s, 3H), 2.48 (s, 3H), 2.24-2.06 (m, 2H), 1.82-1.08 (m, 18H), 1.02-0.86 (m, 5H)。 Example 7 (17)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] Undecane dihydrochloride

TLC: Rf 0.51 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.34-4.20 (m, 4H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.88-3.70 (m, 2H), 3.62-3.46 (m, 4H), 2.72-2.54 (m, 2H), 2.52 (s, 3H), 2.48 (s, 3H), 2.24-2.06 (m, 2H), 1.82-1.08 (m, 18H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ5.02-4.82 (m, 1H), 4.33 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.90-3.70 (m, 2H), 3.64-3.48 (m, 4H), 2.80-2.60 (m, 2H), 2.58 (s, 3H), 2.57 (s, 3H), 2.36-1.08 (m, 25H), 1.04-0.84 (m, 5H)。 Example 7 (18)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] Undecane dihydrochloride

TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 5.02-4.82 (m, 1H), 4.33 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.90-3.70 (m, 2H), 3.64- 3.48 (m, 4H), 2.80-2.60 (m, 2H), 2.58 (s, 3H), 2.57 (s, 3H), 2.36-1.08 (m, 25H), 1.04-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.20（酢酸エチル：メタノール＝３：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.10-4.00 (m, 3H), 4.00-3.00 (m, 16H), 2.65-2.10 (m, 4H), 2.47 (s, 3H), 2.40 (s, 3H), 2.05-1.95 (m, 2H), 1.85-1.15 (m, 15H), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 7 (19)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) propylaminosulfonyl) phenyl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.20 (ethyl acetate: methanol = 3: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.10-4.00 (m, 3H), 4.00 -3.00 (m, 16H), 2.65-2.10 (m, 4H), 2.47 (s, 3H), 2.40 (s, 3H), 2.05-1.95 (m, 2H), 1.85-1.15 (m, 15H), 1.10 -0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.60（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.90 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 4.48 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz,1H), 3.94-3.76 (m, 2H), 3.56-3.36 (m, 4H), 2.71 (s, 6H), 2.56-2.36 (m, 2H), 2.28-2.06 (m, 2H), 1.83-1.10 (m, 15H), 1.08-0.85 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 7 (20)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.60 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.90 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 4.48 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz) , 1H), 3.94-3.76 (m, 2H), 3.56-3.36 (m, 4H), 2.71 (s, 6H), 2.56-2.36 (m, 2H), 2.28-2.06 (m, 2H), 1.83-1.10 (m, 15H), 1.08-0.85 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.59（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.68 (d, J = 8.7 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.73 (m, 2H), 3.60 (t, J = 6.9 Hz, 2H), 3.55-3.34 (m, 4H), 3.45 (t, J = 6.9 Hz, 2H), 2.56-2.36 (m, 2H), 2.27-2.07 (m, 2H), 2.06-1.84 (m, 4H), 1.83-1.10 (m, 15H), 1.06-0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 7 (21)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.59 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.68 (d, J = 8.7 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz) , 1H), 3.92-3.73 (m, 2H), 3.60 (t, J = 6.9 Hz, 2H), 3.55-3.34 (m, 4H), 3.45 (t, J = 6.9 Hz, 2H), 2.56-2.36 ( m, 2H), 2.27-2.07 (m, 2H), 2.06-1.84 (m, 4H), 1.83-1.10 (m, 15H), 1.06-0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.51（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.70-7.62 (m, 4H), 7.22 (d, J = 9.0 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 4.36 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.52-3.40 (m, 4H), 3.30 (s, 6H), 2.62-2.44 (m, 2H), 2.24-2.06 (m, 2H), 1.80-1.14 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (22)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

TLC: Rf 0.51 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.70-7.62 (m, 4H), 7.22 (d, J = 9.0 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 4.36 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.52-3.40 (m, 4H), 3.30 (s, 6H), 2.62-2.44 (m, 2H), 2.24-2.06 (m, 2H), 1.80-1.14 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.91 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 4.42 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.90-3.72 (m, 3H), 3.52-3.36 (m, 4H), 2.56-2.38 (m, 2H), 2.24-2.06 (m, 2H), 2.00-1.10 (m, 25H), 1. 04-0.86 (m, 5H)。 Example 7 (23)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.38 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.91 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 4.42 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz) , 1H), 3.90-3.72 (m, 3H), 3.52-3.36 (m, 4H), 2.56-2.38 (m, 2H), 2.24-2.06 (m, 2H), 2.00-1.10 (m, 25H), 1 04-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.33（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.18 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (m, 1H), 3.94 (s, 3H), 3.94-3.45 (m, 6H), 2.70-2.50 (m, 2H), 2.46 (s, 3H), 2.41 (s, 3H), 2.30-2.10 (m, 2H), 1.85-1.10 (m, 15H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 7 (24)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1,4,9- Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.33 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.18 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (m, 1H), 3.94 (s , 3H), 3.94-3.45 (m, 6H), 2.70-2.50 (m, 2H), 2.46 (s, 3H), 2.41 (s, 3H), 2.30-2.10 (m, 2H), 1.85-1.10 (m , 15H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.18（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.93 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 4.44 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.92-3.74 (m, 2H), 3.58-3.36 (m, 10H), 3.35 (s, 3H), 2.54-2.36 (m, 2H), 2.28-2.06 (m, 2H), 1.94-1.08 (m, 15H), 1.04-0.84 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 7 (25)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.18 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.93 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 4.44 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz) , 1H), 3.92-3.74 (m, 2H), 3.58-3.36 (m, 10H), 3.35 (s, 3H), 2.54-2.36 (m, 2H), 2.28-2.06 (m, 2H), 1.94-1.08 (m, 15H), 1.04-0.84 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.27（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.81 (m, 1H), 8.59 (m, 1H), 8.16-7.94 (m, 2H), 7.71 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 4.40 (s, 2H), 4.06-3.70 (m, 5H), 3.60-3.36 (m, 6H), 3.09 (s, 3H), 2.72-2.42 (m, 2H), 2.26-2.02 (m, 2H), 1.84-1.14 (m, 15H), 1.06-0.84 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 7 (26)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) aminocarbonyl) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.27 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.81 (m, 1H), 8.59 (m, 1H), 8.16-7.94 (m, 2H), 7.71 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 4.40 (s, 2H), 4.06-3.70 (m, 5H), 3.60-3.36 (m, 6H), 3.09 (s, 3H), 2.72-2.42 (m, 2H), 2.26-2.02 (m, 2H), 1.84-1.14 (m, 15H), 1.06-0.84 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.78 (m, 2H), 3.77 (s, 3H), 3.56-3.36 (m, 4H), 2.52-2.34 (m, 2H), 2.26-2.06 (m, 2H), 1.82-1.10 (m, 15H), 1.06-0.84 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 7 (27)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane hydrochloride

TLC: Rf 0.38 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 9.0 Hz, 2H), 7.69 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.92-3.78 (m, 2H), 3.77 (s, 3H) , 3.56-3.36 (m, 4H), 2.52-2.34 (m, 2H), 2.26-2.06 (m, 2H), 1.82-1.10 (m, 15H), 1.06-0.84 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.54（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.90 (s, 3H), 3.88-3.72 (m, 2H), 3.58-3.38 (m, 4H), 2.58-2.38 (m, 2H), 2.28-2.08 (m, 2H), 1.84-1.08 (m, 15H), 1.06-0.86 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 7 (28)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.54 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.05 (dd, J = 7.5, 4.5 Hz, 1H), 3.90 (s, 3H), 3.88-3.72 (m, 2H), 3.58-3.38 (m, 4H), 2.58-2.38 (m, 2H), 2.28-2.08 (m, 2H), 1.84-1.08 (m, 15H), 1.06-0.86 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H) .

ＴＬＣ：Ｒｆ 0.40（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.42 (d, J = 9.0 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J = 7.5, 4.5 Hz, 1H), 3.96-3.76 (m, 2H), 3.88 (s, 3H), 3.68-3.40 (m, 4H), 2.68-2.48 (m, 2H), 2.45 (s, 3H), 2.38 (s, 3H), 2.32-2.08 (m, 2H), 1.84-1.12 (m, 15H), 1.06-0.84 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 7 (29)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] Undecane dihydrochloride

TLC: Rf 0.40 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.42 (d, J = 9.0 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J = 7.5, 4.5 Hz) , 1H), 3.96-3.76 (m, 2H), 3.88 (s, 3H), 3.68-3.40 (m, 4H), 2.68-2.48 (m, 2H), 2.45 (s, 3H), 2.38 (s, 3H ), 2.32-2.08 (m, 2H), 1.84-1.12 (m, 15H), 1.06-0.84 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.18（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ4.58 (m, 1H), 4.21 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.42 (m, 8H), 3.32-3.20 (m, 2H), 2.93 (s, 3H), 2.70-2.50 (m, 2H), 2.50-2.26 (m, 2H), 2.45 (s, 3H), 2.33 (s, 3H), 2.24-2.04 (m, 4H), 1.82-1.06 (m, 15H) , 1.02-0.86 (m, 5H)。 Example 7 (30)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.18 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 4.58 (m, 1H), 4.21 (s, 2H), 4.03 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.42 (m, 8H), 3.32-3.20 ( m, 2H), 2.93 (s, 3H), 2.70-2.50 (m, 2H), 2.50-2.26 (m, 2H), 2.45 (s, 3H), 2.33 (s, 3H), 2.24-2.04 (m, 4H), 1.82-1.06 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.44 (m, 1H), 4.24 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.68 (m, 4H), 3.60-3.40 (m, 4H), 3.02-2.90 (m, 2H), 2.89 (s, 3H), 2.60-2.40 (m, 2H), 2.46 (s, 3H), 2.36 (s, 3H), 2.26-1.96 (m, 6H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H)。 Example 7 (31)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1, 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ4.44 (m, 1H), 4.24 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.92-3.68 (m, 4H), 3.60-3.40 ( m, 4H), 3.02-2.90 (m, 2H), 2.89 (s, 3H), 2.60-2.40 (m, 2H), 2.46 (s, 3H), 2.36 (s, 3H), 2.26-1.96 (m, 6H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.22（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.54-3.43 (m, 2H), 3.27-3.18 (m, 2H), 3.05-2.97 (m, 2H), 2.8 9 (s, 6H), 2.68-2.51 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.28-2.08 (m, 2H), 2.00-1.88 (m, 2H), 1.84-1.10 (m, 15H), 1.04-0.88 (m, 5H)。 Example 7 (32)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) propylaminosulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.22 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 8.02 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz) , 1H), 3.94-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.54-3.43 (m, 2H), 3.27-3.18 (m, 2H), 3.05-2.97 (m, 2H), 2.8 9 (s, 6H), 2.68-2.51 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.28-2.08 (m, 2H), 2.00-1.88 (m, 2H), 1.84- 1.10 (m, 15H), 1.04-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.32（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.67-3.56 (m, 2H), 3.55-3.45 (m, 2H), 3.42 (s, 4H), 3.01 (s, 6H), 2.85 (s, 3H), 2.72-2.53 (m, 2H), 2.50 (s, 3H), 2.41 (s, 3H), 2.27-2.08 (m, 2H), 1.84-1.11 (m, 15H), 1.06-0.84 (m, 5H)。 Example 7 (33)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′, N′- Dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.32 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz) , 1H), 3.94-3.74 (m, 2H), 3.67-3.56 (m, 2H), 3.55-3.45 (m, 2H), 3.42 (s, 4H), 3.01 (s, 6H), 2.85 (s, 3H ), 2.72-2.53 (m, 2H), 2.50 (s, 3H), 2.41 (s, 3H), 2.27-2.08 (m, 2H), 1.84-1.11 (m, 15H), 1.06-0.84 (m, 5H ).

ＴＬＣ：Ｒｆ 0.56（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.68 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz, 1H), 3.92-3.65 (m, 4H), 3.56-3.30 (m, 6H), 2.57-2.36 (m, 2H), 2.26-2.07 (m, 2H), 1.83-1.10 (m, 21H), 1.06-0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 7 (34)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.56 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.68 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.8 Hz) , 1H), 3.92-3.65 (m, 4H), 3.56-3.30 (m, 6H), 2.57-2.36 (m, 2H), 2.26-2.07 (m, 2H), 1.83-1.10 (m, 21H), 1.06 -0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.54（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.69 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.91-3.55 (m, 8H), 3.55-3.30 (m, 6H), 2.57-2.37 (m, 2H), 2.27-2.05 (m, 2H), 1.83-1.08 (m, 15H), 1.06-0.83 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H)。 Example 7 (35)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane. Hydrochloride

TLC: Rf 0.54 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.69 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz) , 1H), 3.91-3.55 (m, 8H), 3.55-3.30 (m, 6H), 2.57-2.37 (m, 2H), 2.27-2.05 (m, 2H), 1.83-1.08 (m, 15H), 1.06 -0.83 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.62 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.16-7.10 (m, 4H), 4.35 (s, 2H), 4.31 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.52-3.38 (m, 4H), 2.86 (s, 6H), 2.62-2.46 (m, 2H), 2.26-2.06 (m, 2H), 1.82-1.12 (m, 15H), 1.06-0.88 (m, 5H)。 Example 7 (36)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.37 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.62 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.16-7.10 (m, 4H), 4.35 (s, 2H), 4.31 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.52-3.38 (m, 4H), 2.86 (s, 6H), 2.62-2.46 (m , 2H), 2.26-2.06 (m, 2H), 1.82-1.12 (m, 15H), 1.06-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.13（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.00 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J = 7.8, 4.8 Hz, 1H), 3.94-3.76 (m, 2H), 3.66-3.56 (m, 2H), 3.52-3.40 (m, 2H), 2.95 (s, 3H), 2.62-2.38 (m, 2H), 2.50 (s, 3H), 2.42 (s, 3H), 2.32-2.10 (m, 2H), 1.84-1.18 (m, 15H), 1.06-0.84 (m, 2H), 0.97 (t, J = 6.9 Hz, 3H)。 Example 7 (37)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.13 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.00 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J = 7.8, 4.8 Hz) , 1H), 3.94-3.76 (m, 2H), 3.66-3.56 (m, 2H), 3.52-3.40 (m, 2H), 2.95 (s, 3H), 2.62-2.38 (m, 2H), 2.50 (s , 3H), 2.42 (s, 3H), 2.32-2.10 (m, 2H), 1.84-1.18 (m, 15H), 1.06-0.84 (m, 2H), 0.97 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.38（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ4.25 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.88-3.73 (m, 2H), 3.59-3.50 (m, 2H), 3.47-3.42 (m, 2H), 2.60 (s, 3H), 2.57-2.45 (m, 2H), 2.38 (s, 3H), 2.23-2.10 (m, 2H), 1.80-1.15 (m, 24H), 1.02-0. 92 (m, 5H)。 Example 7 (38)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.38 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 4.25 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.88-3.73 (m, 2H), 3.59-3.50 (m, 2H), 3.47- 3.42 (m, 2H), 2.60 (s, 3H), 2.57-2.45 (m, 2H), 2.38 (s, 3H), 2.23-2.10 (m, 2H), 1.80-1.15 (m, 24H), 1.02- 0.92 (m, 5H).

ＴＬＣ：Ｒｆ 0.33（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.39-7.29 (m, 5H), 5.14 (s, 2H), 4.52 (m, 1H), 4.33-4.29 (m, 2H), 4.25 (s, 2H), 4.04 (dd, J = 7.8, 4.8 Hz, 1H), 3.87-3.72 (m, 2H), 3.55-3.42 (m, 4H), 3.10-2.98 (m, 2H), 2.60-2.43 (m, 5H), 2.36 (s, 3H), 2.23-1.95 (m, 6H), 1.80-1.15 (m, 15H), 1.02-0.92 (m, 5H)。 Example 7 (39)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.33 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ7.39-7.29 (m, 5H), 5.14 (s, 2H), 4.52 (m, 1H), 4.33-4.29 (m, 2H), 4.25 (s, 2H), 4.04 ( dd, J = 7.8, 4.8 Hz, 1H), 3.87-3.72 (m, 2H), 3.55-3.42 (m, 4H), 3.10-2.98 (m, 2H), 2.60-2.43 (m, 5H), 2.36 ( s, 3H), 2.23-1.95 (m, 6H), 1.80-1.15 (m, 15H), 1.02-0.92 (m, 5H).

ＴＬＣ：Ｒｆ 0.24（クロロホルム：メタノール＝２０：１）；
ＮＭＲ（CD₃OD）：δ7.34 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 4.57 (s, 2H), 4.00 (dd, J = 7.5, 4.5 Hz,1H), 3.55 (s, 2H), 3.47-3.38 (m, 2H), 2.93-2.74 (m, 4H), 2.24-2.04 (m, 2H), 2.00-1.83 (m, 2H), 1.83-1.08 (m, 15H), 1.05-0.84 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 7 (40)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane

TLC: Rf 0.24 (chloroform: methanol = 20: 1);
NMR (CD ₃ OD): δ7.34 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 4.57 (s, 2H), 4.00 (dd, J = 7.5, 4.5 Hz, 1H), 3.55 (s, 2H), 3.47-3.38 (m, 2H), 2.93-2.74 (m, 4H), 2.24-2.04 (m, 2H), 2.00-1.83 (m, 2H), 1.83-1.08 (m, 15H), 1.05-0.84 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H) .

ＮＭＲ（CDCl₃）：δ7.78 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 6.71 (t, J = 4.8 Hz, 1H), 6.32 (brs, 1H), 4.26 (d, J = 4.8 Hz, 2H), 4.00 (m, 1H), 3.81 (s, 3H), 3.64 (s, 2H), 3.54-3.28 (m, 2H), 3.06-2.72 (m, 8H), 2.26-1.10 (m, 15H), 1.06-0.82 (m, 2H), 0.94 (t, J = 6.9 Hz, 3H)。 Example 7 (41)
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane

NMR (CDCl ₃ ): δ 7.78 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 6.71 (t, J = 4.8 Hz, 1H), 6.32 (brs, 1H) , 4.26 (d, J = 4.8 Hz, 2H), 4.00 (m, 1H), 3.81 (s, 3H), 3.64 (s, 2H), 3.54-3.28 (m, 2H), 3.06-2.72 (m, 8H ), 2.26-1.10 (m, 15H), 1.06-0.82 (m, 2H), 0.94 (t, J = 6.9 Hz, 3H).

実施例４（４２）で製造した化合物の代わりに、実施例７（４１）で製造した化合物を用いて、実施例５と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.36（ブタノール：酢酸：水＝４：２：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 4.45 (s, 2H), 4.11 (s, 2H), 4.04 (dd, J = 7.2, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.56-2.34 (m, 2H), 2.30-2.06 (m, 2H), 1.84-1.16 (m, 15H), 1.06-0.86 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 8
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

Using the compound prepared in Example 7 (41) in place of the compound prepared in Example 4 (42), the same operation as in Example 5 was carried out to obtain the compound of the present invention having the following physical property values. .
TLC: Rf 0.36 (butanol: acetic acid: water = 4: 2: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 4.45 (s, 2H), 4.11 (s, 2H), 4.04 (dd , J = 7.2, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.56-2.34 (m, 2H), 2.30-2.06 (m, 2H), 1.84-1.16 (m, 15H), 1.06-0.86 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（３）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−フェニルオキシベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.46（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.50 (d, J = 8.7 Hz, 2H), 7.42-7.37 (m, 2H), 7.18 (m, 1H), 7.07-7.01 (m, 4H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.97 (m, 1H), 3.71 (m, 1H), 3.60-3.05 (m, 5H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenyloxyphenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

Example 2 was repeated using the compound prepared in Reference Example 3 (3) instead of the compound prepared in Reference Example 3 and 4-phenyloxybenzoaldehyde in place of 3-formyl-6-phenyloxypyridine. By the same operation, the compound of the present invention having the following physical properties was obtained.
TLC: Rf 0.46 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.50 (d, J = 8.7 Hz, 2H), 7.42-7.37 (m, 2H), 7.18 (m, 1H), 7.07-7.01 (m, 4H), 4.31 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.97 (m, 1H), 3.71 (m, 1H), 3.60-3.05 (m, 5H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

Examples 9 (1) to 9 (71)
The same operation as in Example 9 was carried out using the corresponding aldehyde derivative instead of 4-phenyloxybenzoaldehyde to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.36（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.28 (d, J = 2.7 Hz, 1H), 8.01 (dd, J = 8.4, 2.7 Hz, 1H), 7.43 (t, J = 8.4 Hz, 2H), 7.25 (t, J = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H), 4.38 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.02 (m, 1H), 3.77 (m, 1H), 3.60-3.05 (m, 5H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (1)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.28 (d, J = 2.7 Hz, 1H), 8.01 (dd, J = 8.4, 2.7 Hz, 1H), 7.43 (t, J = 8.4 Hz, 2H), 7.25 (t , J = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H), 4.38 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H ), 4.02 (m, 1H), 3.77 (m, 1H), 3.60-3.05 (m, 5H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H ), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.54-7.48 (m, 2H), 7.14 (dd, J = 9.6, 8.1 Hz, 2H), 7.09-7.02 (m, 4H), 4.33 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.73 (m, 1H), 3.57-3.40 (m, 3H), 3.33-3.08 (m, 2H), 2.54-1.88 (m, 6H), 1.82-1.63 (m, 5H), 1.48-1.12 (m, 6H), 1.03-0.85 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (2)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-fluorophenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.48 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ7.54-7.48 (m, 2H), 7.14 (dd, J = 9.6, 8.1 Hz, 2H), 7.09-7.02 (m, 4H), 4.33 (s, 2H), 4.15 ( d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.73 (m, 1H), 3.57-3.40 (m, 3H), 3.33-3.08 (m, 2H), 2.54-1.88 (m, 6H) , 1.82-1.63 (m, 5H), 1.48-1.12 (m, 6H), 1.03-0.85 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.58-7.51 (m, 2H), 7.38 (d, J = 9.3 Hz, 2H), 7.09 (brd, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz, 2H), 4.34 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.73 (m, 1H), 3.58-3.40 (m, 3H), 3.32-3.09 (m, 2H), 2.53-1.89 (m, 6H), 1.81-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ7.58-7.51 (m, 2H), 7.38 (d, J = 9.3 Hz, 2H), 7.09 (brd, J = 8.4 Hz, 2H), 7.02 (d, J = 9.3 Hz) , 2H), 4.34 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.73 (m, 1H), 3.58-3.40 (m, 3H), 3.32-3.09 ( m, 2H), 2.53-1.89 (m, 6H), 1.81-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.52（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.74 (d, J = 9.0 Hz, 2H), 7.64-7.58 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.77 (m, 1H), 3.57-3.43 (m, 3H), 3.33-3.08 (m, 2H), 2.54-1.90 (m, 6H), 1.80-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (4)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-cyanophenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.52 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.74 (d, J = 9.0 Hz, 2H), 7.64-7.58 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 9.0 Hz) , 2H), 4.38 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.77 (m, 1H), 3.57-3.43 (m, 3H), 3.33-3.08 ( m, 2H), 2.54-1.90 (m, 6H), 1.80-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.58-3.40 (m, 3H), 3.32-3.03 (m, 2H), 2.95 (s, 3H), 2.52-2.24 (m, 3H), 2.17-1.88 (m, 3H), 1.80-1.62 (m, 5H), 1.48-1.08 (m, 6H), 1.03-0.82 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (5)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J) = 8.7 Hz, 2H), 4.33 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.58-3.40 (m, 3H), 3.32 -3.03 (m, 2H), 2.95 (s, 3H), 2.52-2.24 (m, 3H), 2.17-1.88 (m, 3H), 1.80-1.62 (m, 5H), 1.48-1.08 (m, 6H) , 1.03-0.82 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.21（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.54 (d, J = 3.0 Hz, 1H), 8.08 (m, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 9.0 Hz, 2H), 4.39 (s, 2H), 4.10 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.60-3.20 (m, 5H), 2.73 (s, 3H), 2.70-2.35 (m, 3H), 2.20-1.90 (m, 3H), 1.90-1.60 (m, 5H), 1.50-1.15 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (6)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridin-3-yloxy) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.21 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.54 (d, J = 3.0 Hz, 1H), 8.08 (m, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H) ), 7.28 (d, J = 9.0 Hz, 2H), 4.39 (s, 2H), 4.10 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.60-3.20 (m, 5H), 2.73 (s, 3H), 2.70-2.35 (m, 3H), 2.20-1.90 (m, 3H), 1.90-1.60 (m, 5H), 1.50-1.15 (m, 6H), 1.10 -0.90 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.41（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.45 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.60-3.05 (m, 5H), 2.95 (quint, J = 6.9 Hz, 1H), 2.50-1.90 (m, 6H), 1.85-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.25 (d, J = 6.9 Hz, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 9 (7)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-methylethyl) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.45 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 3.98 (m, 1H), 3.72 (m, 1H), 3.60-3.05 (m, 5H), 2.95 (quint, J = 6.9 Hz, 1H), 2.50-1.90 (m, 6H), 1.85-1.60 ( m, 5H), 1.50-1.10 (m, 6H), 1.25 (d, J = 6.9 Hz, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.32（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.74 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 9.0 Hz, 2H), 7.17 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (dt, J = 3.6, 12.6 Hz, 1H), 3.75 (dt, J = 3.6, 12.6 Hz, 1H), 3.58-3.42 (m, 3H), 3.32-3.13 (m, 2H), 2.80 (s, 3H), 2.54-2.25 (m, 3H), 2.17-1.88 (m, 3H), 1.80-1.63 (m, 5H), 1.49-1.13 (m, 6H), 1.02-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (8)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.32 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.74 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 9.0 Hz, 2H), 7.17 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (dt, J = 3.6, 12.6 Hz, 1H), 3.75 (dt, J = 3.6, 12.6 Hz , 1H), 3.58-3.42 (m, 3H), 3.32-3.13 (m, 2H), 2.80 (s, 3H), 2.54-2.25 (m, 3H), 2.17-1.88 (m, 3H), 1.80-1.63 (m, 5H), 1.49-1.13 (m, 6H), 1.02-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.43（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.45 (d, J = 9.0 Hz, 2H), 7.06 (d, J = 9.0 Hz, 2H), 4.63 (m, 1H), 4.28 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.01-3.90 (m, 3H), 3.72 (m, 1H), 3.63-3.53 (m, 2H), 3.50-3.41 (m, 3H), 3.27 (m, 1H), 3.15( m, 1H), 2.50-1.91 (m, 8H), 1.68-1.65 (m, 7H), 1.39-1.15 (m, 6H), 1.01-0.87 (m, 5H)。 Example 9 (9)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3,4,5,6-tetrahydropyran-4- Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.43 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.45 (d, J = 9.0 Hz, 2H), 7.06 (d, J = 9.0 Hz, 2H), 4.63 (m, 1H), 4.28 (s, 2H), 4.15 (d , J = 2.0 Hz, 1H), 4.01-3.90 (m, 3H), 3.72 (m, 1H), 3.63-3.53 (m, 2H), 3.50-3.41 (m, 3H), 3.27 (m, 1H), 3.15 (m, 1H), 2.50-1.91 (m, 8H), 1.68-1.65 (m, 7H), 1.39-1.15 (m, 6H), 1.01-0.87 (m, 5H).

ＴＬＣ：Ｒｆ 0.75（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.87 (d, J = 7.5 Hz, 2H), 7.81-7.72 (m, 4H), 7.67 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.5 Hz, 2H), 4.48 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.07 (m, 1H), 3.81 (m, 1H), 3.53-3.47 (m, 3H), 3.33-3.17 (m, 2H), 2.51-2.31 (m, 3H), 2.17-1.92 (m, 3H), 1.76-1.70 (m, 5H), 1.40-1.15 (m, 6H), 1.01-0.87 (m, 5H)。 Example 9 (10)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenylcarbonylphenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.75 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ7.87 (d, J = 7.5 Hz, 2H), 7.81-7.72 (m, 4H), 7.67 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.5 Hz) , 2H), 4.48 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.07 (m, 1H), 3.81 (m, 1H), 3.53-3.47 (m, 3H), 3.33-3.17 ( m, 2H), 2.51-2.31 (m, 3H), 2.17-1.92 (m, 3H), 1.76-1.70 (m, 5H), 1.40-1.15 (m, 6H), 1.01-0.87 (m, 5H).

ＴＬＣ：Ｒｆ 0.57（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.39-7.20 (m, 5H), 5.81 (s, 1H), 4.33 (s, 2H), 4.14 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.45-3.41 (m, 3H), 3.26 (m, 1H), 3.10 (m, 1 H), 2.48-1.91 ( m, 6H), 1.80-1.60 (m, 5H), 1.44-1.14 (m, 6H), 1.00-0.86 (m, 5H)。 Example 9 (11)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.57 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.39-7.20 (m, 5H), 5.81 (s, 1H), 4.33 (s, 2H), 4.14 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.45-3.41 (m, 3H), 3.26 (m, 1H), 3.10 ( m, 1H), 2.48-1.91 (m, 6H), 1.80-1.60 (m, 5H), 1.44-1.14 (m, 6H), 1.00-0.86 (m, 5H).

ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.75-3.67 (m, 4H), 3.64-3.49 (m, 3H), 3.35-3.18 (m, 2H), 3.05-2.97 (m, 4H), 2.66-2.34 (m, 3H), 2.49 (s, 3H), 2.40 (s, 3H), 2.20-1.87 (m, 3H), 1.84-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.05-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (12)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine-4- Ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.75-3.67 (m, 4H), 3.64-3.49 (m, 3H), 3.35-3.18 (m, 2H), 3.05-2.97 (m, 4H) ), 2.66-2.34 (m, 3H), 2.49 (s, 3H), 2.40 (s, 3H), 2.20-1.87 (m, 3H), 1.84-1.60 (m, 5H), 1.52-1.10 (m, 6H ), 1.05-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.63-3.53 (m, 3H), 3.34-3.23 (m, 2H), 2.59-2.34 (m, 3H), 2.57 (s, 3H), 2.46 (s, 3H), 2.39 (s, 3H), 2.16 (m, 1H), 2.05-1.93 (m, 2H), 1.77-1.66 (m, 5H), 1.45-1.17 (m, 6H), 1.01-0.88 (m, 5H)。 Example 9 (13)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylaminosulfonylphenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H) ), 4.05 (m, 1H), 3.80 (m, 1H), 3.63-3.53 (m, 3H), 3.34-3.23 (m, 2H), 2.59-2.34 (m, 3H), 2.57 (s, 3H), 2.46 (s, 3H), 2.39 (s, 3H), 2.16 (m, 1H), 2.05-1.93 (m, 2H), 1.77-1.66 (m, 5H), 1.45-1.17 (m, 6H), 1.01- 0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.44（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.98 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.0 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.69 (t, J = 5.7 Hz, 2H), 3.64-3.50 (m, 3H), 3.38-3.24 (m, 2H), 3.19 (t, J = 5.7 Hz, 2H), 2.87 (s, 3H), 2.60-2.34 (m, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.60 (m, 5H), 1.50-1.12 (m, 6H), 1.04-0.82 (m, 5H)。 Example 9 (14)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N-methyl- N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.44 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.98 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.0 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.69 (t, J = 5.7 Hz, 2H), 3.64-3.50 (m, 3H), 3.38-3.24 (m, 2H), 3.19 (t, J = 5.7 Hz, 2H), 2.87 (s, 3H), 2.60-2.34 (m, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.60 (m, 5H), 1.50-1.12 (m, 6H), 1.04-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.40（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ8.51 (d, J = 4.5 Hz, 1H), 8.01 (m, 1H), 7.80 (d, J = 8.0Hz, 1H), 7.41 (m, 1H), 4.32 (s, 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.60-3.49 (m, 3H), 3.33-3.10 (m, 2H), 2.67 (s, 3H ), 2.53-2.35 (m, 3H), 2.41 (s, 3H), 2.16 (m, 1H), 2.05-1.93 (m, 2H), 1.80-1.65 (m, 5H), 1.50-1.15 (m, 6H), 1.01-0.88 (m, 5H)。 Example 9 (15)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (pyridin-2-yl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.40 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 8.51 (d, J = 4.5 Hz, 1H), 8.01 (m, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.41 (m, 1H), 4.32 (s , 2H), 4.16 (d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.60-3.49 (m, 3H), 3.33-3.10 (m, 2H), 2.67 ( s, 3H), 2.53-2.35 (m, 3H), 2.41 (s, 3H), 2.16 (m, 1H), 2.05-1.93 (m, 2H), 1.80-1.65 (m, 5H), 1.50-1.15 ( m, 6H), 1.01-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.34（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ4.32(m, 1H), 4.27 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.73 (m, 1H), 3.60-3.50 (m, 3H), 3.37-3.20 (m, 2H), 2.58-2.40 (m, 9H), 2.13-1.70 (m, 15H), 1.58-1.15 (m, 9H), 1.01-0.88 (m, 5H)。 Example 9 (16)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.34 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 4.32 (m, 1H), 4.27 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.73 (m, 1H), 3.60 -3.50 (m, 3H), 3.37-3.20 (m, 2H), 2.58-2.40 (m, 9H), 2.13-1.70 (m, 15H), 1.58-1.15 (m, 9H), 1.01-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.85 (s, 3H), 3.73 (m, 1H), 3.62-3.56 (m, 3H), 3.40-3.20 (m, 2H), 2.60 (m, 1H), 2.50-2.36 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H), 2.16-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (17)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1, 4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.27 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.85 (s, 3H), 3.73 (m, 1H), 3.62 -3.56 (m, 3H), 3.40-3.20 (m, 2H), 2.60 (m, 1H), 2.50-2.36 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H), 2.16-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.19（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.17(d, J = 2.0 Hz, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.60-3.53 (m, 3H), 3.33-3.27 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.53-2.35 ( m, 3H), 2.42 (s, 3H), 2.39 (s, 3H), 2.17 (m, 1H), 2.05-1.92 (m, 2H), 1.77-1.65 (m, 5H), 1.39-1.15 (m, 6H), 1.01-0.88 (m, 5H)。 Example 9 (18)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N, N- Dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.19 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.62 (d, J = 9.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.0 Hz, 1H) ), 4.05 (m, 1H), 3.80 (m, 1H), 3.60-3.53 (m, 3H), 3.33-3.27 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.53- 2.35 (m, 3H), 2.42 (s, 3H), 2.39 (s, 3H), 2.17 (m, 1H), 2.05-1.92 (m, 2H), 1.77-1.65 (m, 5H), 1.39-1.15 ( m, 6H), 1.01-0.88 (m, 5H).

ＴＬＣ：Ｒｆ 0.47（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.69 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 4.42 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.60-3.10 (m, 5H), 3.46 (s, 6H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 9 (19)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-bismethylsulfonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.47 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.69 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 4.42 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H) ), 4.06 (m, 1H), 3.80 (m, 1H), 3.60-3.10 (m, 5H), 3.46 (s, 6H), 2.55-1.90 (m, 6H), 1.90-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.10-0.90 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.30（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.48-7.38 (m, 4H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.03 (m, 1H), 3.78 (m, 1H), 3.62-3.49 (m, 3H), 3.37-3.21 (m, 2H), 3.04 (s, 3H), 2.62-2.35 (m, 3H), 2.40 (s, 3H), 2.38 (s, 3H), 2.18-1.90 (m, 3H), 1.83-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (20)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylsulfonylaminophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.30 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ7.48-7.38 (m, 4H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.03 (m, 1H), 3.78 (m, 1H) , 3.62-3.49 (m, 3H), 3.37-3.21 (m, 2H), 3.04 (s, 3H), 2.62-2.35 (m, 3H), 2.40 (s, 3H), 2.38 (s, 3H), 2.18 -1.90 (m, 3H), 1.83-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.05 (m, 1H), 3.79 (m, 1H), 3.63-3.48 (m, 3H), 3.34-3.15 (m, 2H), 2.74 (s, 6H), 2.58-2.32 (m, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.21-1.90 (m, 3H), 1.82-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (21)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N, N- Dimethylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.05 (m, 1H), 3.79 (m, 1H), 3.63-3.48 (m, 3H), 3.34-3.15 (m, 2H), 2.74 (s, 6H), 2.58-2.32 (m, 3H), 2.47 (s, 3H), 2.40 (s, 3H), 2.21-1.90 (m, 3H), 1.82-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.72 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.65-3.47 (m, 3H), 3.62 (t, J = 6.6 Hz, 2H), 3.50 (t, J = 6.6 Hz, 2H), 3.33-3.18 (m, 2H), 2.60-2.32 (m, 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.20-1.87 (m, 7H), 1.82-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (22)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine-1- Ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.38 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 7.72 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.65-3.47 (m, 3H), 3.62 (t, J = 6.6 Hz, 2H), 3.50 (t, J = 6.6 Hz, 2H), 3.33 -3.18 (m, 2H), 2.60-2.32 (m, 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.20-1.87 (m, 7H), 1.82-1.62 (m, 5H), 1.48 -1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝９：１）；
ＮＭＲ（CD₃OD）：δ7.65-7.57 (m, 4H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.85-3.46 (m, 12H), 3.34-3.17 (m, 2H), 2.60-2.32 (m, 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.20-1.90 (m, 3H), 1.82-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (23)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine-4- Ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.38 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ7.65-7.57 (m, 4H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.85-3.46 (m, 12H), 3.34-3.17 (m, 2H), 2.60-2.32 (m, 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.20-1.90 (m, 3H), 1.82-1.62 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.40（酢酸エチル：メタノール＝３：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 4.44 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.60-3.38 (m, 3H), 3.30-3.08 (m, 2H), 2.60-2.24 (m, 3H), 2.20-1.86 (m, 3H), 1.82-1.58 (m, 5H), 1.50-1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (24)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-aminocarbonylphenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane hydrochloride

TLC: Rf 0.40 (ethyl acetate: methanol = 3: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 4.44 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.60-3.38 (m, 3H), 3.30-3.08 (m, 2H), 2.60-2.24 (m, 3H), 2.20-1.86 (m, 3H) ), 1.82-1.58 (m, 5H), 1.50-1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.90 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.56-3.42 (m, 3H), 3.33- 2.99 (m, 2H), 2.54-1.88 (m, 6H), 1.81-1.60 (m, 5H), 1.48-1.12 (m, 6H), 1.04-0.81 (m, 5H)。 Example 9 (25)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.90 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.56-3.42 (m, 3H), 3.33 -2.99 (m, 2H), 2.54-1.88 (m, 6H), 1.81-1.60 (m, 5H), 1.48-1.12 (m, 6H), 1.04-0.81 (m, 5H).

ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.89 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.58-3.42 (m, 3H), 3.32- 3.14 (m, 2H), 2.55-2.40 (m, 2H), 2.32 (m, 1H), 2.13 (m, 1H), 2.07-1.89 (m, 2H), 1.82-1.60 (m, 5H), 1.50-1.12 (m, 6H), 1.06-0.80 (m, 5H)。 Example 9 (26)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.89 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.58-3.42 (m, 3H), 3.32 -3.14 (m, 2H), 2.55-2.40 (m, 2H), 2.32 (m, 1H), 2.13 (m, 1H), 2.07-1.89 (m, 2H), 1.82-1.60 (m, 5H), 1.50 -1.12 (m, 6H), 1.06-0.80 (m, 5H).

ＴＬＣ：Ｒｆ 0.62（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.51 (s, 1H), 7.80-7.56 (m, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 4.39 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.62-3.40 (m, 3H), 3.36-3.18 (m, 2H), 2.64-2.30 (m, 3H), 2.63 (s, 3H), 2.20-1.86 (m, 3H), 1.84-1.58 (m, 5H), 1.52-1.08 (m, 6H), 1.04-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (27)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridin-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.62 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.51 (s, 1H), 7.80-7.56 (m, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 4.39 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.62-3.40 (m, 3H), 3.36-3.18 (m, 2H), 2.64-2.30 (m, 3H), 2.63 (s, 3H), 2.20-1.86 (m, 3H), 1.84-1.58 (m, 5H), 1.52-1.08 (m, 6H), 1.04-0.82 (m, 2H ), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.46 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.67-3.39 (m, 3H), 3.27 (m, 1H), 3.15 (m, 1H), 2.53-2.35 (m, 2H), 2.26 (m, 1H), 2.18-1.87 (m, 3H), 1.84-1.60 (m, 5H), 1.51-1.05 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (28)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.46 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.67-3.39 (m, 3H), 3.27 (m, 1H), 3.15 (m, 1H), 2.53-2.35 (m, 2H), 2.26 (m, 1H), 2.18-1.87 (m, 3H), 1.84-1.60 (m, 5H), 1.51-1.05 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.34 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 4.34 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.65-3.50 (m, 3H), 3.32 (m, 1H), 3.29 (m, 1H), 2.64 (m, 1H), 2.55-2.42 (m, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.20-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.52-1.05 (m, 6H), 1.04-0.81 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 9 (29)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.34 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 4.34 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.65-3.50 (m, 3H), 3.32 (m, 1H), 3.29 (m, 1H), 2.64 (m, 1H), 2.55-2.42 ( m, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.20-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.52-1.05 (m, 6H), 1.04-0.81 ( m, 2H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.32（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.71 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.62-3.48 (m, 5H), 3.38-3.18 (m, 2H), 3.01 (t, J = 5.7 Hz, 2H), 2.58-2.30 (m , 3H), 2.46 (s , 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (30)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethyl Aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.32 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.71 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.06 (m, 1H), 3.80 (m, 1H), 3.62-3.48 (m, 5H), 3.38-3.18 (m, 2H), 3.01 (t, J = 5.7 Hz, 2H), 2.58-2.30 ( m, 3H), 2.46 (s, 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 ( m, 5H).

ＴＬＣ：Ｒｆ 0.59（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.06 (m, 1H), 3.80 (m, 1H), 3.62-3.48 (m, 3H), 3.38-3.18 (m, 6H), 2.60-2.30 (m, 3H), 2.47 (s, 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.60 (m, 9H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (31)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine-1- Ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.59 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H) ), 4.06 (m, 1H), 3.80 (m, 1H), 3.62-3.48 (m, 3H), 3.38-3.18 (m, 6H), 2.60-2.30 (m, 3H), 2.47 (s, 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.60 (m, 9H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.52（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.62-7.46 (m, 5H), 4.34 (s, 2H), 4.17 (d, J = 1.8 Hz, 1H), 4.10 (m, 1H), 3.83 (m, 1H), 3.66-3.47 (m, 3H), 3.39-3.13 (m, 2H), 2.60-2.28 (m, 3H), 2.44 (s, 3H), 2.18 (m, 1H), 2.09-1.88 (m, 2H), 1.85-1.62 (m, 5H), 1.54-1.13 (m, 6H), 1.03-0.81 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 9 (32)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (5-chloro-3-methyl-1-phenylpyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.52 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.62-7.46 (m, 5H), 4.34 (s, 2H), 4.17 (d, J = 1.8 Hz, 1H), 4.10 (m, 1H), 3.83 (m, 1H) , 3.66-3.47 (m, 3H), 3.39-3.13 (m, 2H), 2.60-2.28 (m, 3H), 2.44 (s, 3H), 2.18 (m, 1H), 2.09-1.88 (m, 2H) , 1.85-1.62 (m, 5H), 1.54-1.13 (m, 6H), 1.03-0.81 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.49 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 7.02-6.92 (m, 4H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.97 (m, 1H), 3.79 (s, 3H), 3.72 (m, 1H), 3.58-3.38 (m, 3H), 3.30-3.13 (m, 2H), 2.55-2.40 (m, 2H), 2.32 (m, 1H), 2.16-1.86 (m, 3H), 1.81-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.03-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (33)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.49 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 7.02-6.92 (m, 4H), 4.30 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.97 (m, 1H), 3.79 (s, 3H), 3.72 (m, 1H), 3.58-3.38 (m, 3H), 3.30-3.13 (m, 2H), 2.55-2.40 (m, 2H), 2.32 (m, 1H), 2.16-1.86 (m, 3H), 1.81-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.03-0.80 (m, 2H ), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.54 (d, J = 8.7 Hz, 2H), 7.28 (m, 1H), 7.70 (d, J = 8.7 Hz, 2H), 6.75 (ddd, J = 8.7, 2.1, 1.2 Hz, 1H), 6.63-6.56 (m, 2H), 4.33 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.77 (s, 3H), 3.75 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.11 (m, 2H), 2.55-2.23 (m, 3H), 2.17-1.88 (m, 3H), 1.81-1.59 (m, 5H), 1.50-1.06 (m, 6H), 1.03-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (34)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.54 (d, J = 8.7 Hz, 2H), 7.28 (m, 1H), 7.70 (d, J = 8.7 Hz, 2H), 6.75 (ddd, J = 8.7, 2.1, 1.2 Hz, 1H), 6.63-6.56 (m, 2H), 4.33 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.77 (s, 3H), 3.75 ( m, 1H), 3.58-3.40 (m, 3H), 3.30-3.11 (m, 2H), 2.55-2.23 (m, 3H), 2.17-1.88 (m, 3H), 1.81-1.59 (m, 5H), 1.50-1.06 (m, 6H), 1.03-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.43（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.66 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.59-3.42 (m, 3H), 3.30-3.10 (m, 2H), 3.11 (s, 3H), 2.99 (s, 3H), 2.53-2.20 (m, 3H), 2.14 (m, 1H), 2.08-1.88 (m, 2H), 1.83-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (35)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-dimethylaminocarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.43 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.66 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.59-3.42 (m, 3H), 3.30-3.10 (m, 2H), 3.11 (s, 3H), 2.99 (s, 3H), 2.53- 2.20 (m, 3H), 2.14 (m, 1H), 2.08-1.88 (m, 2H), 1.83-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.63-7.43 (m, 5H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.49 (m, 3H), 3.30-3.20 (m, 2H), 2.70-2.30 (m, 9H), 2.20-1.88 (m, 3H), 1.83-1.58 (m, 5H), 1.52-1.06 (m, 6H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (36)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.63-7.43 (m, 5H), 4.32 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H) , 3.64-3.49 (m, 3H), 3.30-3.20 (m, 2H), 2.70-2.30 (m, 9H), 2.20-1.88 (m, 3H), 1.83-1.58 (m, 5H), 1.52-1.06 ( m, 6H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.37 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.63-3.47 (m, 3H), 3.35-3.06 (m, 2H), 2.63-2.26 (m, 3H), 2.43 (s, 3H), 2.38 (s, 3H), 2.35 (s, 3H), 2.16 (m, 1H), 2.09-1.88 (m, 2H), 1.83-1.60 (m, 5H), 1.55-1.10 (m, 6H), 1.08-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (37)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylphenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.37 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.63-3.47 (m, 3H), 3.35-3.06 (m, 2H), 2.63-2.26 (m, 3H), 2.43 (s, 3H), 2.38 (s, 3H), 2.35 (s, 3H), 2.16 (m, 1H), 2.09-1.88 (m, 2H), 1.83-1.60 (m, 5H), 1.55-1.10 (m, 6H), 1.08- 0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.49（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.50 (dd, J = 8.4, 4.8 Hz, 2H), 7.30 (dd, J = 8.4, 8.4 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.63-3.45 (m, 3H), 3.30-3.12 (m, 2H), 2.61-2.30 (m, 3H), 2.37 (s, 3H), 2.36 (s, 3H), 2.16 (m, 1H), 2.08-1.88 (m, 2H), 1.82-1.60 (m, 5H), 1.52-1.07 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (38)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.49 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.50 (dd, J = 8.4, 4.8 Hz, 2H), 7.30 (dd, J = 8.4, 8.4 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.63-3.45 (m, 3H), 3.30-3.12 (m, 2H), 2.61-2.30 (m, 3H), 2.37 (s , 3H), 2.36 (s, 3H), 2.16 (m, 1H), 2.08-1.88 (m, 2H), 1.82-1.60 (m, 5H), 1.52-1.07 (m, 6H), 1.04-0.80 (m , 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.36 (m, 1H), 8.12 (m, 1H), 7.12-6.98 (m, 5H), 4.39 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.81 (s, 3H), 3.74 (m, 1H), 3.60-3.42 (m, 3H), 3.30-3.16 (m, 2H), 2.58-2.30 (m, 3H), 2.16-1.86 (m, 3H), 1.80-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.80 (m, 5H)。 Example 9 (39)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6- (4-methoxyphenyloxy) pyridin-3-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.38 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.36 (m, 1H), 8.12 (m, 1H), 7.12-6.98 (m, 5H), 4.39 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) , 4.00 (m, 1H), 3.81 (s, 3H), 3.74 (m, 1H), 3.60-3.42 (m, 3H), 3.30-3.16 (m, 2H), 2.58-2.30 (m, 3H), 2.16 -1.86 (m, 3H), 1.80-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.80 (m, 5H).

ＴＬＣ：Ｒｆ 0.46（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 9.0 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.25-7.16 (m, 4H), 4.38 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.30-3.10 (m, 2H), 3.11 (s, 3H), 2.54- 2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (40)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.46 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 9.0 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.25-7.16 (m, 4H), 4.38 (s, 2H), 4.15 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.76 (m, 1H), 3.60-3.44 (m, 3H), 3.30-3.10 (m, 2H), 3.11 (s, 3H), 2.54- 2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.15（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.93 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.20-7.08 (m, 4H), 3.98 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.75 (m, 1H), 3.75 (t, J = 5.4 Hz, 2H), 3.58-3.42 (m, 3H), 3.38 (t, J = 5.4 Hz, 2H), 3.30-3.18 (m, 2H), 2.98 (s, 6H), 2.56-2.28 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.46-1.14 (m, 6H), 1.02-0.84 (m, 5H)。 Example 9 (41)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2- (N, N-dimethylamino) Ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.15 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.93 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.20-7.08 (m, 4H), 3.98 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.75 (m, 1H), 3.75 (t, J = 5.4 Hz, 2H), 3.58-3.42 (m, 3H), 3.38 (t, J = 5.4 Hz, 2H), 3.30-3.18 (m, 2H), 2.98 (s, 6H), 2.56-2.28 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H) , 1.46-1.14 (m, 6H), 1.02-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.46（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.73 (t, J = 6.0 Hz, 2H), 3.72-3.48 (m, 5H), 3.30-3.16 (m, 2H), 2.60-2.30 (m , 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.22-1.88 (m, 3H), 1.80-1.62 (m, 5H), 1.50-1.12 (m, 6H), 1.06-0.82 (m, 5H)。 Example 9 (42)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethyl Aminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.46 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H) ), 4.04 (m, 1H), 3.80 (m, 1H), 3.73 (t, J = 6.0 Hz, 2H), 3.72-3.48 (m, 5H), 3.30-3.16 (m, 2H), 2.60-2.30 ( m, 3H), 2.43 (s, 3H), 2.39 (s, 3H), 2.22-1.88 (m, 3H), 1.80-1.62 (m, 5H), 1.50-1.12 (m, 6H), 1.06-0.82 ( m, 5H).

ＴＬＣ：Ｒｆ 0.14（クロロホルム：メタノール：２８％アンモニア水＝２００：２０：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (t, J = 5.7 Hz, 2H), 3.78 (m, 1H), 3.63-3.49 (m, 3H), 3.41 (t, J = 5.7 Hz, 2H), 3.32-3.20 (m, 2H), 3.00 (s, 6H), 2.63-2.35 (m, 3H), 2.45 (s, 3H), 2.39 (s, 3H), 2.20-1.90 (m, 3H), 1.82-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (43)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2- (N , N-Dimethylamino) ethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.14 (chloroform: methanol: 28% aqueous ammonia = 200: 20: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (t, J = 5.7 Hz, 2H), 3.78 (m, 1H), 3.63-3.49 (m, 3H), 3.41 (t, J = 5.7 Hz, 2H), 3.32 -3.20 (m, 2H), 3.00 (s, 6H), 2.63-2.35 (m, 3H), 2.45 (s, 3H), 2.39 (s, 3H), 2.20-1.90 (m, 3H), 1.82-1.63 (m, 5H), 1.48-1.13 (m, 6H), 1.03-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 9.0 Hz, 2H), 7.77 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.12-3.96 (m, 3H), 3.90-3.70 (m, 4H), 3.62-3.48 (m, 6H), 3.20-3.16 (m, 6H), 2.70-2.30 (m, 3H), 2.49 (s, 3H), 2.41 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.04-0.84 (m, 5H)。 Example 9 (44)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2- (morpholine -4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 9.0 Hz, 2H), 7.77 (d, J = 9.0 Hz, 2H), 4.30 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H) ), 4.12-3.96 (m, 3H), 3.90-3.70 (m, 4H), 3.62-3.48 (m, 6H), 3.20-3.16 (m, 6H), 2.70-2.30 (m, 3H), 2.49 (s , 3H), 2.41 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.04-0.84 (m, 5H).

ＴＬＣ：Ｒｆ 0.31（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.58 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.18-7.06 (m, 4H), 4.36 (s, 2H), 4.16 (d, J = 2.4 Hz, 1H), 4.00 (m, 1H), 3.82-3.40 (m, 12H), 3.38-3.12 (m, 2H), 2.52-2.24 (m, 3H), 2.18-1.86 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (45)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.31 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.58 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.18-7.06 (m, 4H), 4.36 (s, 2H), 4.16 (d, J = 2.4 Hz, 1H), 4.00 (m, 1H), 3.82-3.40 (m, 12H), 3.38-3.12 (m, 2H), 2.52-2.24 (m, 3H), 2.18-1.86 (m , 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.05 (d, J = 2.1 Hz, 1H), 7.00-6.90 (m, 2H), 4.26 (s, 4H), 4.23 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 3.94 (m, 1H), 3.68 (m, 1H), 3.58-3.34 (m, 3H), 3.30-3.08 (m, 2H), 2.50-1.86 (m, 6H), 1.80-1.62 ( m, 5H), 1.50-1.04 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (46)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,4-benzodioxan-6-ylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.38 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.05 (d, J = 2.1 Hz, 1H), 7.00-6.90 (m, 2H), 4.26 (s, 4H), 4.23 (s, 2H), 4.15 (d, J = 1.8 Hz, 1H), 3.94 (m, 1H), 3.68 (m, 1H), 3.58-3.34 (m, 3H), 3.30-3.08 (m, 2H), 2.50-1.86 (m, 6H), 1.80-1.62 (m, 5H), 1.50-1.04 (m, 6H), 1.02-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.99 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.06 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.34-3.14 (m, 6H), 2.60-2.30 (m, 3H), 2.45 (s, 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.08 (m, 6H), 1.15 (t, J = 7.5 Hz, 6H), 1.02-0.82 (m, 5H)。 Example 9 (47)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N, N- Diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.99 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.06 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.34-3.14 (m, 6H), 2.60-2.30 (m, 3H), 2.45 (s, 3H), 2.39 (s, 3H), 2.20-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.08 (m, 6H), 1.15 (t, J = 7.5 Hz, 6H), 1.02-0.82 ( m, 5H).

ＴＬＣ：Ｒｆ 0.10（酢酸エチル：メタノール＝３：１）；
ＮＭＲ（CD₃OD）：δ8.48-8.37 (m, 2H), 7.73 (d, J = 9.0 Hz, 2H), 7.73-7.60 (m, 2H), 7.31 (d, J = 9.0 Hz, 2H), 4.39 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.60-3.20 (m, 5H), 2.70-2.40 (m, 3H), 2.20-1.90 (m, 3H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H), 1.10-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (48)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (pyridin-1-oxide-3-yloxy) phenylmethyl) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.10 (ethyl acetate: methanol = 3: 1);
NMR (CD ₃ OD): δ 8.48-8.37 (m, 2H), 7.73 (d, J = 9.0 Hz, 2H), 7.73-7.60 (m, 2H), 7.31 (d, J = 9.0 Hz, 2H) , 4.39 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.60-3.20 (m, 5H), 2.70-2.40 (m, 3H ), 2.20-1.90 (m, 3H), 1.90-1.60 (m, 5H), 1.60-1.10 (m, 6H), 1.10-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.34（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.01 (d, J = 8.7 Hz, 2H), 7.85 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.10-3.94 (m, 3H), 3.78 (m, 1H), 3.66-3.56 (m, 5H), 3.40-3.20 (m, 4H), 2.91 (s, 3H), 2.88-2.72 (m, 2H), 2.70-2.40 (m, 3H), 2.50 (s, 3H), 2.40 (s, 3H), 2.20-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.56-1.10 (m, 6H), 1.04-0.82 (m, 5H)。 Example 9 (49)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (4-methylpiperazine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.34 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.01 (d, J = 8.7 Hz, 2H), 7.85 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H) ), 4.10-3.94 (m, 3H), 3.78 (m, 1H), 3.66-3.56 (m, 5H), 3.40-3.20 (m, 4H), 2.91 (s, 3H), 2.88-2.72 (m, 2H ), 2.70-2.40 (m, 3H), 2.50 (s, 3H), 2.40 (s, 3H), 2.20-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.56-1.10 (m, 6H ), 1.04-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.44（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.60-3.44 (m, 3H), 3.28- 3.16 (m, 2H), 2.91 (s, 3H), 2.52-2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H), 1.02-0.82 (m, 5H)。 Example 9 (50)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.44 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J) = 9.0 Hz, 2H), 4.36 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.74 (m, 1H), 3.60-3.44 (m, 3H), 3.28 -3.16 (m, 2H), 2.91 (s, 3H), 2.52-2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.82-1.62 (m, 5H), 1.50-1.10 (m, 6H) , 1.02-0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.63（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.56 (m, 1H), 7.33-7.16 (m, 2H), 4.32 (s, 2H), 4.18 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.30-3.16 (m, 2H), 2.62-1.88 (m, 6H), 2.39 (s, 3H), 2.28 (s, 3H), 1.84-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 6.9 Hz, 3H)。 Example 9 (51)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2,4-difluorophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.63 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ7.56 (m, 1H), 7.33-7.16 (m, 2H), 4.32 (s, 2H), 4.18 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H) , 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.30-3.16 (m, 2H), 2.62-1.88 (m, 6H), 2.39 (s, 3H), 2.28 (s, 3H), 1.84 -1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.21（クロロホルム：メタノール：２８％アンモニア水＝１００：１０：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.50 (m, 3H), 3.40-3.22 (m, 6H), 2.96 (s, 6H), 2.74-2.38 (m, 3H), 2.49 (s, 3H), 2.41 (s, 3H), 2.22-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (52)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2- (N , N-Dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane / 3 hydrochloride

TLC: Rf 0.21 (chloroform: methanol: 28% aqueous ammonia = 100: 10: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 8.7 Hz, 2H), 7.78 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.50 (m, 3H), 3.40-3.22 (m, 6H), 2.96 (s, 6H), 2.74-2.38 (m, 3H), 2.49 (s, 3H), 2.41 (s, 3H), 2.22-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.52-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.21（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.98 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.49 (m, 3H), 3.37-3.20 (m, 2H), 2.94 (s, 3H), 2.63-2.33 (m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.16 (m, 1H), 2.09-1.90 (m, 2H), 1.83-1.62 (m, 5H), 1.50-1.12 (m, 6H), 1.04-0.82 (m, 5H)。 Example 9 (53)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.21 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.98 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 4.31 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.49 (m, 3H), 3.37-3.20 (m, 2H), 2.94 (s, 3H), 2.63-2.33 (m, 3H), 2.43 (s, 3H), 2.40 (s, 3H), 2.16 (m, 1H), 2.09-1.90 (m, 2H), 1.83-1.62 (m, 5H), 1.50-1.12 (m, 6H), 1.04- 0.82 (m, 5H).

ＴＬＣ：Ｒｆ 0.43（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.05 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.40 (m, 3H), 3.30-3.10 (m, 2H), 2.56-1.86 (m, 6H), 1.82-1.60 (m, 5H), 1.52-1.16 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 9 (54)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.43 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.05 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.38 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.60-3.40 (m, 3H), 3.30 -3.10 (m, 2H), 2.56-1.86 (m, 6H), 1.82-1.60 (m, 5H), 1.52-1.16 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.33（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.77 (s, 3H), 3.77 (m, 1H), 3.58-3.38 (m, 3H), 3.30-3.10 (m, 2H), 2.54-2.22 (m, 3H), 2.18-1.86 (m, 3H), 1.82-1.60 (m, 5H), 1.50-1.08 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 9 (55)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.33 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.52 (s, 2H), 4.43 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.77 (s, 3H), 3.77 (m , 1H), 3.58-3.38 (m, 3H), 3.30-3.10 (m, 2H), 2.54-2.22 (m, 3H), 2.18-1.86 (m, 3H), 1.82-1.60 (m, 5H), 1.50 -1.08 (m, 6H), 1.04-0.80 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.27（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.93 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 4.43 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.60-3.40 (m, 7H), 3.35 (s, 3H), 3.30-3.10 (m, 2H), 2.58-1.60 (m, 13H), 1.52-1.08 (m, 6H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (56)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.27 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.93 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 4.43 (s, 2H), 4.16 (d, J = 1.8 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.60-3.40 (m, 7H), 3.35 (s, 3H), 3.30-3.10 (m, 2H), 2.58-1.60 (m, 13H), 1.52-1.08 (m, 6H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.22（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.80 (m, 1H), 8.57 (m, 1H), 8.08 (m, 1H), 7.96 (m, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06-3.90 (m, 3H), 3.80 (m, 1H), 3.62-3.38 (m, 5H), 3.30-3.10 (m, 2H), 3.08 (s, 3H), 2.64-2.30 (m, 3H), 2.18-1.84 (m, 3H), 1.82-1.60 (m, 5H), 1.50-1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (57)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N-methyl-N- (2- (pyridine-2 -Yl) ethyl) aminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.22 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.80 (m, 1H), 8.57 (m, 1H), 8.08 (m, 1H), 7.96 (m, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 4.40 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.06-3.90 (m, 3H), 3.80 (m, 1H), 3.62-3.38 ( m, 5H), 3.30-3.10 (m, 2H), 3.08 (s, 3H), 2.64-2.30 (m, 3H), 2.18-1.84 (m, 3H), 1.82-1.60 (m, 5H), 1.50- 1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.41（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.59-7.56 (m, 4H), 7.15 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.60-3.46 (m, 7H), 3.30-3.13 (m, 2H), 2.51-2.11 (m, 4H), 2.04-1.89 (m, 6H), 1.80-1.65 (m, 5H), 1.50-1.15 (m, 6H), 1.00-0.87 (m, 5H)。 Example 9 (58)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ7.59-7.56 (m, 4H), 7.15 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.60-3.46 (m, 7H), 3.30-3.13 (m, 2H), 2.51-2.11 (m, 4H ), 2.04-1.89 (m, 6H), 1.80-1.65 (m, 5H), 1.50-1.15 (m, 6H), 1.00-0.87 (m, 5H).

ＴＬＣ：Ｒｆ 0.51（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.58 (d, J = 9.0 Hz, 2H), 7.49 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.30-3.16 (m, 2H), 2.62-2.32 (m, 3H), 2.40 (s, 3H), 2.39 (s, 3H), 2.22-1.86 (m, 3H), 1.84-1.60 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 9 (59)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-chlorophenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.51 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.58 (d, J = 9.0 Hz, 2H), 7.49 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.78 (m, 1H), 3.62-3.48 (m, 3H), 3.30-3.16 (m, 2H), 2.62-2.32 (m, 3H), 2.40 (s, 3H), 2.39 (s, 3H), 2.22-1.86 (m, 3H), 1.84-1.60 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.88 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.18 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.30-3.16 (m, 2H), 2.62-2.28 (m, 3H), 2.46 (s, 3H), 2.40 (s, 3H), 2.24-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.56-1.06 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 9 (60)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-trifluoromethylphenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.88 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.18 (d, J = 2.1 Hz, 1H) ), 4.04 (m, 1H), 3.80 (m, 1H), 3.64-3.46 (m, 3H), 3.30-3.16 (m, 2H), 2.62-2.28 (m, 3H), 2.46 (s, 3H), 2.40 (s, 3H), 2.24-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.56-1.06 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.44（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.40 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.18 (d, J = 2.4 Hz, 1H), 4.04 (m, 1H), 3.88 (s, 3H), 3.80 (m, 1H), 3.66-3.48 (m, 3H), 3.30-3.18 (m, 2H), 2.64-2.30 (m, 3H), 2.42 (s, 3H), 2.36 (s, 3H), 2.22-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Example 9 (61)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.44 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.40 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.18 (d, J = 2.4 Hz, 1H) ), 4.04 (m, 1H), 3.88 (s, 3H), 3.80 (m, 1H), 3.66-3.48 (m, 3H), 3.30-3.18 (m, 2H), 2.64-2.30 (m, 3H), 2.42 (s, 3H), 2.36 (s, 3H), 2.22-1.88 (m, 3H), 1.84-1.60 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.27（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.28 (s, 2H), 4.23 (q, J = 7.2 Hz, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.64-3.44 (m, 3H), 3.30-3.18 (m, 2H), 2.70-2.34 (m, 3H), 2.48 (s, 3H), 2.43 (s, 3H), 2.22-1.86 (m, 3H), 1.84-1.60 (m, 5H), 1.52-1.08 (m, 6H), 1.43 (t, J = 7.2 Hz, 3H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (62)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.27 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.28 (s, 2H), 4.23 (q, J = 7.2 Hz, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.00 (m, 1H), 3.78 (m , 1H), 3.64-3.44 (m, 3H), 3.30-3.18 (m, 2H), 2.70-2.34 (m, 3H), 2.48 (s, 3H), 2.43 (s, 3H), 2.22-1.86 (m , 3H), 1.84-1.60 (m, 5H), 1.52-1.08 (m, 6H), 1.43 (t, J = 7.2 Hz, 3H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.31（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.28 (s, 2H), 4.16 (d, J = 2.4 Hz, 1H), 4.15 (t, J = 7.2 Hz, 2H), 4.00 (m, 1H), 3.76 (m, 1H), 3.62-3.46 (m, 3H), 3.30-3.18 (m, 2H), 2.66-2.36 (m, 3H), 2.47 (s, 3H), 2.43 (s, 3H), 2.20-1.60 (m, 10H), 1.52-1.10 (m, 6H), 1.18 (t, J = 7.2 Hz, 3H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 9 (63)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.31 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.28 (s, 2H), 4.16 (d, J = 2.4 Hz, 1H), 4.15 (t, J = 7.2 Hz, 2H), 4.00 (m, 1H), 3.76 (m , 1H), 3.62-3.46 (m, 3H), 3.30-3.18 (m, 2H), 2.66-2.36 (m, 3H), 2.47 (s, 3H), 2.43 (s, 3H), 2.20-1.60 (m , 10H), 1.52-1.10 (m, 6H), 1.18 (t, J = 7.2 Hz, 3H), 1.06-0.80 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.33（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.26 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.62-3.46 (m, 3H), 3.30-3.22 (m, 2H), 2.64-2.40 (m, 3H), 2.63 (s, 3H), 2.42 (s, 3H), 2.20-1.86 (m, 3H), 1.84-1.62 (m, 5H), 1.72 (s, 9H), 1.54-1.16 (m, 6H), 1.04-0.82 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 9 (64)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1,1-dimethylethyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.33 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.26 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.62-3.46 (m, 3H) , 3.30-3.22 (m, 2H), 2.64-2.40 (m, 3H), 2.63 (s, 3H), 2.42 (s, 3H), 2.20-1.86 (m, 3H), 1.84-1.62 (m, 5H) , 1.72 (s, 9H), 1.54-1.16 (m, 6H), 1.04-0.82 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.33（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.27 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.64-3.44 (m, 4H), 3.30-3.20 (m, 2H), 2.66-2.36 (m, 3H), 2.47 (s, 3H), 2.42 (s, 3H), 2.28-1.60 (m, 16H), 1.58-1.10 (m, 6H), 1.08-0.82 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 9 (65)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.33 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.27 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.78 (m, 1H), 3.64-3.44 (m, 4H) , 3.30-3.20 (m, 2H), 2.66-2.36 (m, 3H), 2.47 (s, 3H), 2.42 (s, 3H), 2.28-1.60 (m, 16H), 1.58-1.10 (m, 6H) , 1.08-0.82 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.36-7.18 (m, 3H), 7.16-7.00 (m, 2H), 4.39 (t, J = 6.3 Hz, 2H), 4.18 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 3.88 (m, 1H), 3.72-3.46 (m, 2H), 3.42-3.22 (m, 4H), 3.12 (t, J = 6.3 Hz, 2H), 2.66-2.34 (m, 3H), 2.44 (s, 3H), 2.18-1.86 (m, 3H), 1.92 (s, 3H), 1.84-1.62 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m, 2H), 0.97 (t, J = 6.9 Hz, 3H)。 Example 9 (66)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2-phenylethyl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.36-7.18 (m, 3H), 7.16-7.00 (m, 2H), 4.39 (t, J = 6.3 Hz, 2H), 4.18 (s, 2H), 4.17 (d, J = 2.4 Hz, 1H), 3.88 (m, 1H), 3.72-3.46 (m, 2H), 3.42-3.22 (m, 4H), 3.12 (t, J = 6.3 Hz, 2H), 2.66-2.34 (m , 3H), 2.44 (s, 3H), 2.18-1.86 (m, 3H), 1.92 (s, 3H), 1.84-1.62 (m, 5H), 1.54-1.10 (m, 6H), 1.06-0.82 (m , 2H), 0.97 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.40（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.42-7.25 (m, 5H), 5.14 (s, 2H), 4.56 (m, 1H), 4.36-4.25 (m, 2H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.62-3.45 (m, 3H), 3.40-3.20 (m, 2H), 3.18-2.94 (m, 2H), 2.67-2.30 (m, 9H), 2.20-1.85 (m, 7H), 1.83-1.58 (m, 5H), 1.50-1.08 (m, 6H), 1.05-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (67)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidine- 4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.40 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.42-7.25 (m, 5H), 5.14 (s, 2H), 4.56 (m, 1H), 4.36-4.25 (m, 2H), 4.25 (s, 2H), 4.15 ( d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.62-3.45 (m, 3H), 3.40-3.20 (m, 2H), 3.18-2.94 (m, 2H) , 2.67-2.30 (m, 9H), 2.20-1.85 (m, 7H), 1.83-1.58 (m, 5H), 1.50-1.08 (m, 6H), 1.05-0.80 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.92 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 4.42 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.92-3.69 (m, 2H), 3.60-3.39 (m, 3H), 3.30-3.12 (m, 2H), 2.56-2.26 (m, 3H), 2.17-1.58 (m, 14H), 1.51-1.08 (m, 10H), 1.06-0.80 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 9 (68)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.45 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.92 (d, J = 8.7 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 4.42 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H) ), 4.02 (m, 1H), 3.92-3.69 (m, 2H), 3.60-3.39 (m, 3H), 3.30-3.12 (m, 2H), 2.56-2.26 (m, 3H), 2.17-1.58 (m , 14H), 1.51-1.08 (m, 10H), 1.06-0.80 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.26（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.48 (m, 1H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.05-3.83 (m, 3H), 3.74 (m, 1H), 3.60-3.46 (m, 3H), 3.40-3.20 (m, 2H), 3.05-2.92 (m, 2H), 2.90 (s, 3H), 2.60 (m, 1H), 2.52-2.40 (m, 2H), 2.49 (s, 3H), 2.39 (s, 3H), 2.26-1.88 (m, 7H), 1.84-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.05-0.80 (m, 2H), 0.95 (t, J = 6.9 Hz, 3H)。 Example 9 (69)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-methylsulfonylpiperidine-4) -Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.26 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ4.48 (m, 1H), 4.25 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.05-3.83 (m, 3H), 3.74 (m, 1H) , 3.60-3.46 (m, 3H), 3.40-3.20 (m, 2H), 3.05-2.92 (m, 2H), 2.90 (s, 3H), 2.60 (m, 1H), 2.52-2.40 (m, 2H) , 2.49 (s, 3H), 2.39 (s, 3H), 2.26-1.88 (m, 7H), 1.84-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.05-0.80 (m, 2H) , 0.95 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ7.89 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.71 (t, J = 5.7 Hz, 2H), 3.60-3.40 (m, 3H), 3.51 (t, J = 5.7 Hz, 2H), 3.30-3.10 (m, 2H), 2.58-1.84 (m, 6H), 1.82-1.56 (m, 5H), 1.54-1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 9 (70)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.50 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 7.89 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.17 (d, J = 2.1 Hz, 1H), 4.02 (m, 1H), 3.78 (m, 1H), 3.71 (t, J = 5.7 Hz, 2H ), 3.60-3.40 (m, 3H), 3.51 (t, J = 5.7 Hz, 2H), 3.30-3.10 (m, 2H), 2.58-1.84 (m, 6H), 1.82-1.56 (m, 5H), 1.54-1.06 (m, 6H), 1.04-0.80 (m, 2H), 0.96 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.34 (d, J = 8.7 Hz, 4H), 6.97 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 4.57 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 3.71 (s, 2H), 3.47 (m, 1H), 3.35 (dd, J = 9.0, 2.1 Hz, 1H), 3.30-2.88 (m, 5H), 2.31-1.81 (m, 6H), 1.81-1.58 (m, 5H), 1.55-1.05 (m, 6H), 1.05-0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 9 (71)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane

TLC: Rf 0.37 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ7.34 (d, J = 8.7 Hz, 4H), 6.97 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 4.57 (s, 2H) ), 4.13 (d, J = 2.1 Hz, 1H), 3.71 (s, 2H), 3.47 (m, 1H), 3.35 (dd, J = 9.0, 2.1 Hz, 1H), 3.30-2.88 (m, 5H) , 2.31-1.81 (m, 6H), 1.81-1.58 (m, 5H), 1.55-1.05 (m, 6H), 1.05-0.83 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（９）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−メチルスルホニルアミノフェニルオキシ）ベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.54（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.54 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, j = 8.4 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.55-3.43 (m, 3H), 3.30- 3.16 (m, 2H), 2.95 (s, 3H), 2.52-2.28 (m, 3H), 2.14-1.91 (m, 3H), 1.76-1.65 (m, 5H), 1.50-1.15 (m, 6H), 1.00-0.86 (m, 5H)。 Example 10
(3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (9) was replaced with 4- (4-methylsulfonylaminophenyloxy) benzoaldehyde in place of 3-formyl-6-phenyloxypyridine. Using the same procedure as in Example 2, a compound of the present invention having the following physical data was obtained.
TLC: Rf 0.54 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.54 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, j = 8.4 Hz, 2H), 7.03 (d, J) = 8.7 Hz, 2H), 4.32 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 3.98 (m, 1H), 3.73 (m, 1H), 3.55-3.43 (m, 3H), 3.30 -3.16 (m, 2H), 2.95 (s, 3H), 2.52-2.28 (m, 3H), 2.14-1.91 (m, 3H), 1.76-1.65 (m, 5H), 1.50-1.15 (m, 6H) , 1.00-0.86 (m, 5H).

参考例３で製造した化合物の代わりに、参考例３（４）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−ホルミル−３，５−ジメチル−１−フェニルピラゾールを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.31（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.67-7.56 (m, 5H), 4.37 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 4.06 (m, 1H), 3.98-3.91 (m, 2H), 3.80 (m, 1H), 3.64-3.53 (m, 4H), 3.46-3.37 (m, 3H), 2.80-2.52 (m, 5H), 2.45 (s, 3H), 2. 16-2.01 (m, 2H), 1.91-1.82 (m, 2H), 1.71 (m, 1H), 1.50-1.17 (m, 6H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 11
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (3 , 5-Dimethyl-1-phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (4) was replaced with 4-formyl-3,5-dimethyl-1-phenylpyrazole instead of 3-formyl-6-phenyloxypyridine. And the same operation as in Example 2 was carried out to obtain a compound of the present invention having the following physical data.
TLC: Rf 0.31 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.67-7.56 (m, 5H), 4.37 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 4.06 (m, 1H), 3.98-3.91 (m, 2H), 3.80 (m, 1H), 3.64-3.53 (m, 4H), 3.46-3.37 (m, 3H), 2.80-2.52 (m, 5H), 2.45 (s, 3H), 2.16-2.01 ( m, 2H), 1.91-1.82 (m, 2H), 1.71 (m, 1H), 1.50-1.17 (m, 6H), 0.95 (t, J = 7.5 Hz, 3H).

Examples 11 (1) to 11 (5)
The same operation as in Example 11 was carried out using the corresponding aldehyde derivative instead of 4-formyl-3,5-dimethyl-1-phenylpyrazole to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.28（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.06-3.90 (m, 3H), 3.75 (m, 1H), 3.56-3.34 (m, 5H), 3.30-3.20 (m, 2H), 2.91 (s, 3H), 2.51-2.28 (m, 3H), 2.16-1.69 (m, 5H), 1.50-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 11 (1)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (4 -(4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.28 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J) = 8.7 Hz, 2H), 4.36 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.06-3.90 (m, 3H), 3.75 (m, 1H), 3.56-3.34 (m, 5H) , 3.30-3.20 (m, 2H), 2.91 (s, 3H), 2.51-2.28 (m, 3H), 2.16-1.69 (m, 5H), 1.50-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.11 (d, J = 2.0 Hz, 1H), 4.04-3.91 (m, 3H), 3.76 (m, 1H), 3.76 (s, 3H), 3.56-3.37 (m, 5H), 3.30-3.13 (m, 2H), 2.50-1.70 (m, 8H), 1.39-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 11 (2)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (4 -(4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.11 (d, J = 2.0 Hz, 1H), 4.04-3.91 (m, 3H), 3.76 (m, 1H), 3.76 (s, 3H), 3.56-3.37 (m, 5H), 3.30-3.13 (m, 2H), 2.50-1.70 (m, 8H), 1.39-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz , 3H).

ＴＬＣ：Ｒｆ 0.55（クロロホルム：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.63 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H), 4.06 (m, 1H), 4.00-3.91 (m, 2H), 3.79 (m, 1H), 3.63-3.52 (m, 4H), 3.46-3.34 (m, 3H), 3.13 (s, 3H), 3.04 (s, 3H), 2.62-2.37 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.15 (m, 1H), 2.03 (m, 1H), 1.90-1.70 (m, 3H), 1.50-1.15 (m, 6H), 0.96 (t, J = 7.0 Hz, 3H)。 Example 11 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (3 , 5-Dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.55 (chloroform: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.63 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 4.32 (s, 2H), 4.13 (d, J = 2.0 Hz, 1H) ), 4.06 (m, 1H), 4.00-3.91 (m, 2H), 3.79 (m, 1H), 3.63-3.52 (m, 4H), 3.46-3.34 (m, 3H), 3.13 (s, 3H), 3.04 (s, 3H), 2.62-2.37 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.15 (m, 1H), 2.03 (m, 1H), 1.90-1.70 (m, 3H), 1.50-1.15 (m, 6H), 0.96 (t, J = 7.0 Hz, 3H).

ＴＬＣ：Ｒｆ 0.30（クロロホルム：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.08-3.93 (m, 3H), 3.75 (m, 1H), 3.57-3.34 (m, 5H), 3.30-3.15 (m, 2H), 2.52-1.69 (m, 8H), 1.50-1.18 (m, 5H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 11 (4)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (4 -(4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.30 (chloroform: methanol = 4: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.08-3.93 (m, 3H), 3.75 (m, 1H), 3.57-3.34 (m, 5H) , 3.30-3.15 (m, 2H), 2.52-1.69 (m, 8H), 1.50-1.18 (m, 5H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.35（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 4.33 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.04-3.92 (m, 3H), 3.72 (m, 1H), 3.54-3.38 (m, 5H), 3.30-3.13 (m, 2H), 2.95 (s, 3H), 2.51-2.26 (m, 3H), 2.16-2.00 (m, 2H), 1.89-1.70 (m, 3H), 1.50-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 11 (5)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9- (4 -(4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.35 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J) = 8.7 Hz, 2H), 4.33 (s, 2H), 4.12 (d, J = 2.0 Hz, 1H), 4.04-3.92 (m, 3H), 3.72 (m, 1H), 3.54-3.38 (m, 5H) , 3.30-3.13 (m, 2H), 2.95 (s, 3H), 2.51-2.26 (m, 3H), 2.16-2.00 (m, 2H), 1.89-1.70 (m, 3H), 1.50-1.15 (m, 5H), 0.95 (t, J = 7.0 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（５）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−ホルミル−３，５−ジメチル−１−フェニルピラゾールを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.45（酢酸エチル：メタノール＝４：１）；
ＮＭＲ（CD₃OD）：δ7.64-7.51 (m, 5H), 4.34 (s, 2H), 4.05 (m, 1H), 4.01 (d, J = 2.0 Hz, 1H), 3.79 (m, 1H), 3.63-3.52 (m, 3H), 3.39 (dd, J = 9.9, 2.0 Hz, 1H), 3.30 (m, 1H), 2.64 (m, 1H), 2.48 (m, 1H), 2.47 (s, 3H), 2.42 (s, 3H), 2.37-2.12 (m, 2H), 1.90-1.82 (m, 2H), 1.74-1.15 (m, 11H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 12
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (5) was replaced with 4-formyl-3,5-dimethyl-1-phenylpyrazole instead of 3-formyl-6-phenyloxypyridine. And the same operation as in Example 2 was carried out to obtain a compound of the present invention having the following physical data.
TLC: Rf 0.45 (ethyl acetate: methanol = 4: 1);
NMR (CD ₃ OD): δ7.64-7.51 (m, 5H), 4.34 (s, 2H), 4.05 (m, 1H), 4.01 (d, J = 2.0 Hz, 1H), 3.79 (m, 1H) , 3.63-3.52 (m, 3H), 3.39 (dd, J = 9.9, 2.0 Hz, 1H), 3.30 (m, 1H), 2.64 (m, 1H), 2.48 (m, 1H), 2.47 (s, 3H ), 2.42 (s, 3H), 2.37-2.12 (m, 2H), 1.90-1.82 (m, 2H), 1.74-1.15 (m, 11H), 0.96 (t, J = 7.5 Hz, 3H).

Examples 12 (1) to 12 (3)
The same operation as in Example 12 was carried out using the corresponding aldehyde derivative instead of 4-formyl-3,5-dimethyl-1-phenylpyrazole to obtain the following compound of the present invention.

ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.96 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.52 (s, 2H), 4.42 (s, 2H), 4.02 (m, 1H), 4.00 (d, J = 1.8 Hz, 1H), 3.77 (s, 3H), 3.77 (m, 1H), 3.60-3.02 (m, 5H), 2.58-2.04 (m, 5H), 2.00-1.06 (m, 12H), 0.96 (t, J = 7.5 Hz, 3H)。 Example 12 (1)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.96 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 4.52 (s, 2H), 4.42 (s, 2H), 4.02 (m, 1H), 4.00 (d, J = 1.8 Hz, 1H), 3.77 (s, 3H), 3.77 (m , 1H), 3.60-3.02 (m, 5H), 2.58-2.04 (m, 5H), 2.00-1.06 (m, 12H), 0.96 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.85 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.02 (m, 1H), 4.01 (d, J = 2.1 Hz, 1H), 3.78 (m, 1H), 3.40-3.12 (m, 5H), 2.92 (s, 3H), 2.60-2.06 (m, 5H), 2.00-1.08 (m, 12H), 0.96 (t, J = 7.2 Hz, 3H)。 Example 12 (2)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.85 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 7.08 (d, J) = 8.7 Hz, 2H), 4.37 (s, 2H), 4.02 (m, 1H), 4.01 (d, J = 2.1 Hz, 1H), 3.78 (m, 1H), 3.40-3.12 (m, 5H), 2.92 (s, 3H), 2.60-2.06 (m, 5H), 2.00-1.08 (m, 12H), 0.96 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝５：１）；
ＮＭＲ（CD₃OD）：δ8.05 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.38 (s, 2H), 4.02 (m, 1H), 4.01 (d, J = 1.8 Hz, 1H), 3.78 (m, 1H), 3.62-3.08 (m, 5H), 2.60-2.06 (m, 5H), 2.00-1.08 (m, 12H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 12 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 5: 1);
NMR (CD ₃ OD): δ 8.05 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.38 (s, 2H), 4.02 (m, 1H), 4.01 (d, J = 1.8 Hz, 1H), 3.78 (m, 1H), 3.62-3.08 (m, 5H), 2.60 -2.06 (m, 5H), 2.00-1.08 (m, 12H), 0.96 (t, J = 6.9 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（６）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−メチルアミノカルボニルフェニルオキシ）ベンズアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.99 (m, 1H), 3.74 (m, 1H), 3.55-3.40 (m, 3H), 3.20 (m, 1H), 3.19 (dd, J = 9.6, 1.8 Hz, 1H), 2.91 (s, 3H), 2.59-2.29 (m, 3H), 2.12 (m, 1H), 2.00 (m, 1H), 1.74 (m, 1H), 1.46 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 13
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (6) was replaced with 4- (4-methylaminocarbonylphenyloxy) benzaldehyde in place of 3-formyl-6-phenyloxypyridine. The same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.07 (d, J) = 9.0 Hz, 2H), 4.36 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 3.99 (m, 1H), 3.74 (m, 1H), 3.55-3.40 (m, 3H), 3.20 (m, 1H), 3.19 (dd, J = 9.6, 1.8 Hz, 1H), 2.91 (s, 3H), 2.59-2.29 (m, 3H), 2.12 (m, 1H), 2.00 (m, 1H), 1.74 (m, 1H), 1.46 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H).

Examples 13 (1) and 13 (2)
The same operation as in Example 13 was carried out using the corresponding aldehyde derivative instead of 4- (4-methylaminocarbonylphenyloxy) benzaldehyde to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.39（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.40 (m, 1H), 4.30 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.59-3.43 (m, 3H), 3.22 (m, 1H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 2.66 (m, 1H), 2.53 (s, 3H), 2.49 (s, 3H), 2.50-2.38 (m, 2H), 2.15-1.10 (m, 14H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 13 (1)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.39 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.40 (m, 1H), 4.30 (s, 2H), 4.14 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.59 -3.43 (m, 3H), 3.22 (m, 1H), 3.20 (dd, J = 9.6, 2.1 Hz, 1H), 2.66 (m, 1H), 2.53 (s, 3H), 2.49 (s, 3H), 2.50-2.38 (m, 2H), 2.15-1.10 (m, 14H), 0.99 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz , 3H).

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.95 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.76 (s, 3H), 3.54-3.39 (m, 3H), 3.19 (m, 1H), 3.18 (dd, J = 9.6, 2.1 Hz, 1H), 2.58-2.26 (m, 3H), 2.10 (m, 1H), 1.99 (m, 1H), 1.72 (m, 1H), 1.46 (m, 1H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.92 (t, J = 7.5 Hz, 3H)。 Example 13 (2)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.95 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.42 (s, 2H), 4.13 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.76 (s , 3H), 3.54-3.39 (m, 3H), 3.19 (m, 1H), 3.18 (dd, J = 9.6, 2.1 Hz, 1H), 2.58-2.26 (m, 3H), 2.10 (m, 1H), 1.99 (m, 1H), 1.72 (m, 1H), 1.46 (m, 1H), 0.98 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.92 (t, J = 7.5 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（７）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−メチルアミノカルボニルフェニルオキシ）ベンズアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.38（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.15 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.75 (m, 1H), 3.54-3.39 (m, 3H), 3.30-3.10 (m, 2H), 2.91 (s, 3H), 2.56-2.27 (m, 3H), 2.18-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.46 (m, 1H), 1.37-1.11 (m, 3H), 1.04-0.80 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 14
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (7) was replaced with 4- (4-methylaminocarbonylphenyloxy) benzaldehyde in place of 3-formyl-6-phenyloxypyridine. The same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.38 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.15 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 3.99 (m, 1H), 3.75 (m, 1H), 3.54-3.39 (m, 3H), 3.30 -3.10 (m, 2H), 2.91 (s, 3H), 2.56-2.27 (m, 3H), 2.18-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.46 (m, 1H), 1.37 -1.11 (m, 3H), 1.04-0.80 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H).

Examples 14 (1) to 14 (5)
The same operation as in Example 14 was carried out using the corresponding aldehyde derivative instead of 4- (4-methylaminocarbonylphenyloxy) benzaldehyde to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.39 (m, 1H), 4.29 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60-3.42 (m, 3H), 3.40-3.20 (m, 2H), 2.65 (m, 1H), 2.53 (s, 3H), 2.49 (s, 3H), 2.53-2.35 (m, 2H), 2.15-1.05 (m, 22H), 1.05-0.80 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H)。 Example 14 (1)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)- 1,4,9-Triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.39 (m, 1H), 4.29 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60 -3.42 (m, 3H), 3.40-3.20 (m, 2H), 2.65 (m, 1H), 2.53 (s, 3H), 2.49 (s, 3H), 2.53-2.35 (m, 2H), 2.15-1.05 (m, 22H), 1.05-0.80 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.94 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.41 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.76 (s, 3H), 3.54-3.38 (m, 3H), 3.27 (dd, J = 9.6, 1.8 Hz, 1H), 3.18 (m, 1H), 2.57-2.26 (m, 3H), 2.16-1.86 (m, 3H), 1.82-1.60 (m, 5H), 1.54-1.05 (m, 4H), 1.03-0.80 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H)。 Example 14 (2)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.94 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 4.51 (s, 2H), 4.41 (s, 2H), 4.14 (d, J = 1.8 Hz, 1H), 4.01 (m, 1H), 3.76 (m, 1H), 3.76 (s , 3H), 3.54-3.38 (m, 3H), 3.27 (dd, J = 9.6, 1.8 Hz, 1H), 3.18 (m, 1H), 2.57-2.26 (m, 3H), 2.16-1.86 (m, 3H ), 1.82-1.60 (m, 5H), 1.54-1.05 (m, 4H), 1.03-0.80 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.63 (s, 4H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.64-3.43 (m, 3H), 3.34-3.20 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.62 (m, 1H), 2.53-2.39 (m, 2H), 2.45 (s, 3H), 2.44 (s, 3H), 2.19-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.46 (m, 1H), 1.38-1.10 (m, 3H), 1.05-0.80 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 14 (3)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N, N- Dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.63 (s, 4H), 4.32 (s, 2H), 4.16 (d, J = 2.1 Hz, 1H), 4.04 (m, 1H), 3.79 (m, 1H), 3.64 -3.43 (m, 3H), 3.34-3.20 (m, 2H), 3.13 (s, 3H), 3.04 (s, 3H), 2.62 (m, 1H), 2.53-2.39 (m, 2H), 2.45 (s , 3H), 2.44 (s, 3H), 2.19-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.46 (m, 1H), 1.38-1.10 (m, 3H), 1.05-0.80 (m , 2H), 0.95 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.21（クロロホルム：メタノール：酢酸＝２０：２：１）；
ＮＭＲ（CD₃OD）：δ8.04 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.55-3.38 (m, 3H), 3.30-3.09 (m, 2H), 2.55-2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.57-1.10 (m, 4H), 1.04-0.80 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 14 (4)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.21 (chloroform: methanol: acetic acid = 20: 2: 1);
NMR (CD ₃ OD): δ 8.04 (d, J = 9.0 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.01 (m, 1H), 3.75 (m, 1H), 3.55-3.38 (m, 3H), 3.30 -3.09 (m, 2H), 2.55-2.26 (m, 3H), 2.18-1.88 (m, 3H), 1.83-1.60 (m, 5H), 1.57-1.10 (m, 4H), 1.04-0.80 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.54（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.88 (s, 3H), 3.75 (m, 1H), 3.54-3.41 (m, 3H), 3.30-3.10 (m, 2H), 2.58-2.27 (m, 3H), 2.18-1.87 (m, 3H), 1.84-1.61 (m, 5H), 1.56-1.08 (m, 4H), 1.04-0.80 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H)。 Example 14 (5)
(3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.54 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.37 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.88 (s, 3H), 3.75 (m, 1H), 3.54-3.41 (m, 3H), 3.30-3.10 (m, 2H), 2.58-2.27 (m, 3H), 2.18-1.87 (m, 3H), 1.84-1.61 (m, 5H), 1.56-1.08 (m, 4H) , 1.04-0.80 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H).

実施例４（４２）で製造した化合物の代わりに、実施例１４（５）で製造した化合物を用いて、実施例５と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.42（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.03 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 5.87 (d, J = 10.5 Hz, 1H), 4.37 (s, 2H), 3.78-3.62 (m, 2H), 3.58-3.38 (m, 4H), 2.54-2.36 (m, 3H), 2.27-2.15 (m, 2H), 1.80-1.51 (m, 7H), 1.50-1.08 (m, 5H), 0.93 (t, J = 7.2 Hz, 3H)。 Example 15
(3R) -1-propyl-2,5-dioxo-3- (1-cyclohexylmethylidene) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane hydrochloride

Using the compound prepared in Example 14 (5) in place of the compound prepared in Example 4 (42), the same operation as in Example 5 was carried out to obtain the compound of the present invention having the following physical properties. .
TLC: Rf 0.42 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.03 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 5.87 (d, J = 10.5 Hz, 1H), 4.37 (s, 2H), 3.78-3.62 (m, 2H), 3.58-3.38 (m, 4H), 2.54-2.36 (m, 3H), 2.27-2.15 (m, 2H), 1.80-1.51 (m, 7H), 1.50-1.08 (m, 5H), 0.93 (t, J = 7.2 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、相当するアミノ酸誘導体を、ｎ−ブチルアミンの代わりに、相当するアミン誘導体を、３−ホルミル−６−フェニルオキシピリジンの代わりに、相当するアルデヒド誘導体用いて、参考例１→参考例２→実施例１→参考例３→実施例２と同様の操作をし、以下に示した化合物を得た。
ＴＬＣ：Ｒｆ 0.51（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.39-4.27 (m, 1H), 4.28 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.68 (m, 2H), 3.61-3.50 (m, 2H), 3.47-3.38 (m, 2H), 2.68-2.50 (m, 2H), 2.49 (s, 3H), 2.45 (s, 3H), 2.25-2.05 (m, 2H), 2.03-1.20 (m, 15H), 0.98-0.89 (m, 9H)。 Example 16
(3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, the corresponding amino acid derivative is used, and instead of n-butylamine, the corresponding amine derivative is used, Reference Example 1 → Reference Example 2 → Example 1 → Reference Example 3 → Using the corresponding aldehyde derivative instead of formyl-6-phenyloxypyridine, the same operation as in Example 2 was carried out to obtain the compound shown below. Obtained.
TLC: Rf 0.51 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.39-4.27 (m, 1H), 4.28 (s, 2H), 4.01 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.68 (m, 2H), 3.61- 3.50 (m, 2H), 3.47-3.38 (m, 2H), 2.68-2.50 (m, 2H), 2.49 (s, 3H), 2.45 (s, 3H), 2.25-2.05 (m, 2H), 2.03- 1.20 (m, 15H), 0.98-0.89 (m, 9H).

Examples 16 (1) to 16 (6)
The same operation as in Example 16 was carried out using the corresponding aldehyde derivative instead of 1-cyclohexyl-4-formyl-3,5-dimethylpyrazole to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.53（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 4.34 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.69 (m, 2H), 3.55-3.43 (m, 2H), 3.39-3.30 (m, 2H), 2.95 (s, 3H), 2.48-2.29 (m, 2H), 2.28-2.09 (m, 2H), 1.90-1.44 (m, 5H), 0.94 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 16 (1)
(3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5 .5] Undecane hydrochloride

TLC: Rf 0.53 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 7.03 (d, J) = 9.0 Hz, 2H), 4.34 (s, 2H), 4.01 (dd, J = 7.8, 4.8 Hz, 1H), 3.90-3.69 (m, 2H), 3.55-3.43 (m, 2H), 3.39-3.30 ( m, 2H), 2.95 (s, 3H), 2.48-2.29 (m, 2H), 2.28-2.09 (m, 2H), 1.90-1.44 (m, 5H), 0.94 (d, J = 6.6 Hz, 3H) , 0.93 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.09（クロロホルム：メタノール：酢酸＝１０：５：１）；
ＮＭＲ（CD₃OD）：δ8.07 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz, 1H), 3.95-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.50-3.40 (m, 2H), 3.35-3.20 (m, 4H), 2.95 (s, 6H), 2.72-2.53 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.30-2.08 (m, 2H), 1.92-1.45 (m, 5H), 0.99-0.89 (m, 9H)。 Example 16 (2)
(3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) ethylamino Sulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane trihydrochloride

TLC: Rf 0.09 (chloroform: methanol: acetic acid = 10: 5: 1);
NMR (CD ₃ OD): δ 8.07 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J = 7.8, 4.5 Hz) , 1H), 3.95-3.73 (m, 2H), 3.66-3.56 (m, 2H), 3.50-3.40 (m, 2H), 3.35-3.20 (m, 4H), 2.95 (s, 6H), 2.72-2.53 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.30-2.08 (m, 2H), 1.92-1.45 (m, 5H), 0.99-0.89 (m, 9H).

ＴＬＣ：Ｒｆ 0.57（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.43-4.25 (m, 1H), 4.29 (s, 2H), 4.04 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.60-3.50 (m, 2H), 3.48-3.38 (m, 2H), 2.70-2.50 (m, 2H), 2.51 (s, 3H), 2.47 (s, 3H), 2.25-2.03 (m, 2H), 2.03-1.40 (m, 19H), 1.40-1.08 (m, 4H), 1.05-0.83 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 16 (3)
(3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] Undecane dihydrochloride

TLC: Rf 0.57 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ4.43-4.25 (m, 1H), 4.29 (s, 2H), 4.04 (dd, J = 7.8, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.60- 3.50 (m, 2H), 3.48-3.38 (m, 2H), 2.70-2.50 (m, 2H), 2.51 (s, 3H), 2.47 (s, 3H), 2.25-2.03 (m, 2H), 2.03- 1.40 (m, 19H), 1.40-1.08 (m, 4H), 1.05-0.83 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.55（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 9.0 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.89-3.69 (m, 2H), 3.54-3.43 (m, 2H), 3.39-3.30 (m, 2H), 2.95 (s, 3H), 2.50-2.30 (m, 2H), 2.28-2.06 (m, 2H), 1.83-1.40 (m, 10H), 1.40-1.10 (m, 3H), 1.05-0.85 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H)。 Example 16 (4)
(3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.55 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.53 (d, J = 9.0 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 4.33 (s, 2H), 4.04 (dd, J = 7.5, 4.5 Hz, 1H), 3.89-3.69 (m, 2H), 3.54-3.43 (m, 2H), 3.39-3.30 ( m, 2H), 2.95 (s, 3H), 2.50-2.30 (m, 2H), 2.28-2.06 (m, 2H), 1.83-1.40 (m, 10H), 1.40-1.10 (m, 3H), 1.05- 0.85 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.48（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.54 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 3.97 (s, 2H), 3.77-3.62 (m, 2H), 3.55-3.35 (m, 4H), 2.95 (s, 3H), 2.48-2.33 (m, 2H), 2.33-2.22 (m, 2H), 1.60-1.46 (m, 2H), 1.43-1.26 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 16 (5)
1-butyl-2,5-dioxo-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.48 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.54 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.03 (d, J) = 8.7 Hz, 2H), 4.32 (s, 2H), 3.97 (s, 2H), 3.77-3.62 (m, 2H), 3.55-3.35 (m, 4H), 2.95 (s, 3H), 2.48-2.33 ( m, 2H), 2.33-2.22 (m, 2H), 1.60-1.46 (m, 2H), 1.43-1.26 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.50（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.34 (m, 1H), 4.27 (s, 2H), 3.97 (s, 2H), 3.78-3.65 (m, 2H), 3.62-3.47 (m, 4H), 2.65-2.50 (m, 2H), 2.50 (s, 3H), 2.45 (s, 3H), 2.31-2.20 (m, 2H), 2.04-1.70 (m, 6H), 1.65-1.42 (m, 4H), 1.42-1.20 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H)。 Example 16 (6)
1-butyl-2,5-dioxo-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.50 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.34 (m, 1H), 4.27 (s, 2H), 3.97 (s, 2H), 3.78-3.65 (m, 2H), 3.62-3.47 (m, 4H), 2.65- 2.50 (m, 2H), 2.50 (s, 3H), 2.45 (s, 3H), 2.31-2.20 (m, 2H), 2.04-1.70 (m, 6H), 1.65-1.42 (m, 4H), 1.42- 1.20 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシル−３−ヒドロキシプロパン酸を、ｎ−ブチルアミンの代わりに、２−ブチニルアミンを、Ｎ−ベンジル−４−ピペリドンの代わりに、Ｎ−（３，５−ジメチル−１−フェニルピラゾール−４−イル）メチル−４−ピペリドン、ベンジルイソニトリルの代わりに、ｎ−ブチルイソニトリルを用いて、参考例１→参考例２→実施例１と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.60-7.45 (m, 5H), 4.44-4.28 (m, 3H), 4.21 (d, J = 2.1 Hz, 1H), 4.10-3.94 (m, 2H), 3.79 (m, 1H), 3.66-3.54 (m, 2H), 3.32 (m, 1H), 2.74 (m, 1H), 2.56-2.34 (m, 8H), 2.24 (m, 1H), 2.08-1.90 (m, 2H), 1.84-1.62 (m, 7H), 1.44-1.12 (m, 3H), 1.05-0.82 (m, 2H)。 Example 17
(3R) -1- (2-butynyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, (2R, 3R) -2- (t-butoxycarbonylamino) -3-cyclohexyl-3 -Hydroxypropanoic acid, 2-butynylamine in place of n-butylamine and N- (3,5-dimethyl-1-phenylpyrazol-4-yl) methyl-4 in place of N-benzyl-4-piperidone. -Reference Example 1 → Reference Example 2 → The same operation as in Example 1 was performed using n-butyl isonitrile instead of piperidone and benzyl isonitrile to obtain the compound of the present invention having the following physical property values.
TLC: Rf 0.45 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.60-7.45 (m, 5H), 4.44-4.28 (m, 3H), 4.21 (d, J = 2.1 Hz, 1H), 4.10-3.94 (m, 2H), 3.79 ( m, 1H), 3.66-3.54 (m, 2H), 3.32 (m, 1H), 2.74 (m, 1H), 2.56-2.34 (m, 8H), 2.24 (m, 1H), 2.08-1.90 (m, 2H), 1.84-1.62 (m, 7H), 1.44-1.12 (m, 3H), 1.05-0.82 (m, 2H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシル−３−ヒドロキシプロパン酸の代わりに、（２Ｓ，３Ｓ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシル−３−ヒドロキシプロパン酸を用いて、実施例１７と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.60-7.45 (m, 5H), 4.44-4.28 (m, 3H), 4.21 (d, J = 2.1 Hz, 1H), 4.10-3.94 (m, 2H), 3.79 (m, 1H), 3.66-3.54 (m, 2H), 3.32 (m, 1H), 2.74 (m, 1H), 2.56-2.34 (m, 8H), 2.24 (m, 1H), 2.08-1.90 (m, 2H), 1.84-1.62 (m, 7H), 1.44-1.12 (m, 3H), 1.05-0.82 (m, 2H)。 Example 17 (1)
(3S) -1- (2-butynyl) -2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-cyclohexyl-3-hydroxypropanoic acid, (2S, 3S) -2- (t-butoxycarbonylamino) -3-cyclohexyl-3 The same operation as in Example 17 was carried out using -hydroxypropanoic acid to obtain a compound of the present invention having the following physical data.
TLC: Rf 0.45 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.60-7.45 (m, 5H), 4.44-4.28 (m, 3H), 4.21 (d, J = 2.1 Hz, 1H), 4.10-3.94 (m, 2H), 3.79 ( m, 1H), 3.66-3.54 (m, 2H), 3.32 (m, 1H), 2.74 (m, 1H), 2.56-2.34 (m, 8H), 2.24 (m, 1H), 2.08-1.90 (m, 2H), 1.84-1.62 (m, 7H), 1.44-1.12 (m, 3H), 1.05-0.82 (m, 2H).

PS-TsCl-HL樹脂（商品名、Argonaut Technologies社、カタログ番号800366）（３０５ｍｇ）に２−（４−フェニルオキシフェニル）エチルアルコール（１１２ｍｇ）のジクロロメタン（２ｍｌ）、ピリジン（２ｍｌ）溶液を加えた。反応混合物を室温で５時間撹拌した。樹脂をジクロロメタンで３回、ジメチルホルムアミドで５回、ジメチルホルムアミド：水＝３：１で５回、テトラヒドロフランで３回、ジクロロメタンで３回、アセトニトリルで３回洗浄した。得られた樹脂に、参考例３（２）で製造した化合物（１１６ｍｇ）のアセトニトリル（５ｍｌ）溶液とジイソプロピルエチルアミン（0.366ｍｌ）を加えた。反応混合物を７０℃で１８時間撹拌した。放冷後、アセトニトリルで樹脂を洗浄し、得られた洗浄液を濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル：メタノール＝２０：１）によって精製し、さらに塩酸で処理することによって、以下の物性値を有する本発明化合物（８２ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.54（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.37-7.29 (m, 4H), 7.11(t, J = 7.2 Hz, 1H), 6.97-6.95 (m, 4H), 4.06 (d, J = 7.5, 4.5 Hz, 1H), 3.88-3.77 (m, 2H), 3.65 (m, 2H), 3.46-3.36 (m, 4H), 3.13-3.07 (m, 2H), 2.48 (m, 2H), 2.28-2.14 (m, 2H) ,1.80-1.21(m, 15H), 0.98 (t, J = 7.0 Hz, 3H), 0.99-0.91 (m, 2H)。 Example 18
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

To PS-TsCl-HL resin (trade name, Argonaut Technologies, catalog number 800366) (305 mg), a solution of 2- (4-phenyloxyphenyl) ethyl alcohol (112 mg) in dichloromethane (2 ml) and pyridine (2 ml) was added. . The reaction mixture was stirred at room temperature for 5 hours. The resin was washed three times with dichloromethane, five times with dimethylformamide, five times with dimethylformamide: water = 3: 1, three times with tetrahydrofuran, three times with dichloromethane, and three times with acetonitrile. To the obtained resin, a solution of the compound (116 mg) produced in Reference Example 3 (2) in acetonitrile (5 ml) and diisopropylethylamine (0.366 ml) were added. The reaction mixture was stirred at 70 ° C. for 18 hours. After cooling, the resin was washed with acetonitrile, and the obtained washing liquid was concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate: methanol = 20: 1), and further treated with hydrochloric acid to give the compound of the present invention (82 mg) having the following physical data.
TLC: Rf 0.54 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.37-7.29 (m, 4H), 7.11 (t, J = 7.2 Hz, 1H), 6.97-6.95 (m, 4H), 4.06 (d, J = 7.5, 4.5 Hz, 1H), 3.88-3.77 (m, 2H), 3.65 (m, 2H), 3.46-3.36 (m, 4H), 3.13-3.07 (m, 2H), 2.48 (m, 2H), 2.28-2.14 (m, 2H), 1.80-1.21 (m, 15H), 0.98 (t, J = 7.0 Hz, 3H), 0.99-0.91 (m, 2H).

Example 18 (1) and 18 (2)
Instead of 2- (4-phenyloxyphenyl) ethyl alcohol, the corresponding alcohol derivative was prepared using the compound prepared in Reference Example 3 (1) in place of the compound prepared in Reference Example 3 (2). The same operation as in Example 18 was carried out to obtain the compound of the present invention shown below.

ＴＬＣ：Ｒｆ 0.37（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.37-7.29 (m, 4H), 7.11(t, J = 7.5 Hz, 1H), 6.98-6.95 (m, 4H), 4.03 (d, J = 7.5, 4.5 Hz, 1H), 3.89-3.77 (m, 2H), 3.64 (m, 2H), 3.42-3.32 (m, 4H), 3.12-3.07 (m, 2H), 2.45 (m, 2H), 2.29-2.16 (m, 2H), 1.88-1.36 (m, 7H), 0.98 (t, J = 7.0 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 18 (1)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5.5] Undecane hydrochloride

TLC: Rf 0.37 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ7.37-7.29 (m, 4H), 7.11 (t, J = 7.5 Hz, 1H), 6.98-6.95 (m, 4H), 4.03 (d, J = 7.5, 4.5 Hz, 1H), 3.89-3.77 (m, 2H), 3.64 (m, 2H), 3.42-3.32 (m, 4H), 3.12-3.07 (m, 2H), 2.45 (m, 2H), 2.29-2.16 (m, 2H), 1.88-1.36 (m, 7H), 0.98 (t, J = 7.0 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.22 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 4.01 (d, J = 7.5, 4.5 Hz, 1H), 3.87-3.77 (m, 2H), 3.77 (s, 3H), 3.63 (m, 2H), 3.43-3.32 (m, 4H), 3.03 (m, 2H), 2.44 (m, 2H), 2.28-2.15 (m, 2H), 1.85-1.36(m, 7H), 0.97 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H)。 Example 18 (2)
(3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-methoxyphenyl) ethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.37 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.22 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 4.01 (d, J = 7.5, 4.5 Hz, 1H), 3.87-3.77 (m, 2H), 3.77 (s, 3H), 3.63 (m, 2H), 3.43-3.32 (m, 4H), 3.03 (m, 2H), 2.44 (m, 2H), 2.28-2.15 (m, 2H ), 1.85-1.36 (m, 7H), 0.97 (t, J = 7.5 Hz, 3H), 0.95 (d, J = 6.3 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H).

参考例３（２）で製造した化合物（１８６ｍｇ）のジメチルスルホキシド（３ｍｌ）溶液に、エチル ４−フルオロベンゾエート（１６４ｍｇ）と炭酸カリウム（１４１ｍｇ）を加えた。反応混合物を１４０℃で２４時間撹拌した。反応混合物に水を加え、ｔ−ブチルメチルエーテルで抽出した。抽出物を飽和塩化ナトリウム水溶液で洗浄し、無水硫酸マグネシウムで乾燥し、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝４：１→３：１）によって精製し、さらに４Ｎ塩化水素酢酸エチル溶液で処理し、以下の物性値を有する本発明化合物（６７ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.27（ヘキサン：酢酸エチル＝２：１）；
ＮＭＲ（CD₃OD）：δ8.13 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.37 (q, J = 7.2 Hz, 2H), 4.31-4.15 (m, 2H), 4.07 (dd, J = 7.5, 4.5 Hz, 1H), 3.85-3.75 (m, 2H), 3.47-3.38 (m, 2H), 2.67-2.50 (m, 2H), 2.30-2.12 (m, 2H), 1.85-1.46 (m, 10H), 1.44-1.19 (m, 5H), 1.38 (t, J = 7.2 Hz, 3H), 1.05-0.88 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H)。 Example 19
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-ethoxycarbonylphenyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

Ethyl 4-fluorobenzoate (164 mg) and potassium carbonate (141 mg) were added to a solution of the compound (186 mg) produced in Reference Example 3 (2) in dimethyl sulfoxide (3 ml). The reaction mixture was stirred at 140 ° C. for 24 hours. Water was added to the reaction mixture, and extracted with t-butyl methyl ether. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1 → 3: 1), and further treated with a 4N solution of hydrogen chloride in ethyl acetate to give the compound of the present invention (67 mg) having the following physical data. Got.
TLC: Rf 0.27 (hexane: ethyl acetate = 2: 1);
NMR (CD ₃ OD): δ 8.13 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 4.37 (q, J = 7.2 Hz, 2H), 4.31-4.15 (m , 2H), 4.07 (dd, J = 7.5, 4.5 Hz, 1H), 3.85-3.75 (m, 2H), 3.47-3.38 (m, 2H), 2.67-2.50 (m, 2H), 2.30-2.12 (m , 2H), 1.85-1.46 (m, 10H), 1.44-1.19 (m, 5H), 1.38 (t, J = 7.2 Hz, 3H), 1.05-0.88 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、（３Ｓ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシルプロパン酸を、Ｎ−ベンジル−４−ピペリドンの代わりに、Ｎ−ベンジルオキシカルボニル−４−ピペリドンを用いて、参考例１→参考例２→実施例１と同様の操作をし、以下の物性値を有する標題化合物を得た。
ＴＬＣ：Ｒｆ 0.35（ヘキサン：酢酸エチル＝１：１）；
ＮＭＲ（CD₃OD）：δ7.39-7.31 (m, 5H), 6.48 (brs, 1H), 5.16 (s, 2H), 4.15 (brs, 2H), 4.00 (ddd, J = 9.6, 4.8, 1.5 Hz, 1H), 3.76-3.16 (m, 4H), 2.02-1.12 (m, 19H), 1.08-0.88 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H)。 Reference example 4
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-benzyloxycarbonyl-1,4,9-triazaspiro [5.5] undecane

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, (3S) -2- (t-butoxycarbonylamino) -3-cyclohexylpropanoic acid is Reference Example 1 → Reference Example 2 → The same operation as in Example 1 was performed using N-benzyloxycarbonyl-4-piperidone instead of N-benzyl-4-piperidone, to give the title compound having the following physical data. Got.
TLC: Rf 0.35 (hexane: ethyl acetate = 1: 1);
NMR (CD ₃ OD): δ7.39-7.31 (m, 5H), 6.48 (brs, 1H), 5.16 (s, 2H), 4.15 (brs, 2H), 4.00 (ddd, J = 9.6, 4.8, 1.5) Hz, 1H), 3.76-3.16 (m, 4H), 2.02-1.12 (m, 19H), 1.08-0.88 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H).

参考例４で製造した化合物（１ｇ）のジメチルホルムアミド（２０ｍｌ）溶液に、氷冷下、６０％水素化ナトリウム（１６４ｍｇ）を加えた。混合物を室温で１時間撹拌した。混合物に氷冷下、ヨウ化メチル（0.3ｍｌ）を加えた。反応混合物を室温で一晩撹拌した。反応混合物に、氷水を加え、酢酸エチルで抽出した。抽出物を水、飽和塩化ナトリウム水溶液で洗浄し、無水硫酸マグネシウムで乾燥し、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝２：１）によって精製し、以下の物性値を有する標題化合物（１ｇ）を得た。
ＴＬＣ：Ｒｆ 0.34（ヘキサン：酢酸エチル＝１：１）；
ＮＭＲ（CD₃OD）：δ7.40-7.32 (m, 5H), 5.16 (s, 2H), 4.12 (brs, 2H), 3.91 (t, J = 5.7 Hz, 1H), 3.88 (brs, 1H), 3.49 (m, 1H), 3.35 (m, 1H), 2.92 (s, 3H), 2.90 (m, 1H), 2.04-1.10 (m, 19H), 1.04-0.82 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H)。 Reference example 5
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-4-methyl-9-benzyloxycarbonyl-1,4,9-triazaspiro [5.5] undecane

To a solution of the compound (1 g) produced in Reference Example 4 in dimethylformamide (20 ml) was added 60% sodium hydride (164 mg) under ice-cooling. The mixture was stirred at room temperature for 1 hour. Methyl iodide (0.3 ml) was added to the mixture under ice cooling. The reaction mixture was stirred overnight at room temperature. Ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound (1 g) having the following physical data.
TLC: Rf 0.34 (hexane: ethyl acetate = 1: 1);
NMR (CD ₃ OD): δ7.40-7.32 (m, 5H), 5.16 (s, 2H), 4.12 (brs, 2H), 3.91 (t, J = 5.7 Hz, 1H), 3.88 (brs, 1H) , 3.49 (m, 1H), 3.35 (m, 1H), 2.92 (s, 3H), 2.90 (m, 1H), 2.04-1.10 (m, 19H), 1.04-0.82 (m, 2H), 0.92 (t , J = 7.2 Hz, 3H).

参考例５で製造した化合物（１ｇ）のメタノール（２０ｍｌ）溶液に、１０％パラジウム炭素（６０ｍｇ）を加えた。反応混合物を水素ガス雰囲気下、室温で８時間撹拌した。反応混合物をセライト（商品名）を用いて、ろ過し、ろ液に４Ｎ塩化水素酢酸エチル溶液を加えて、濃縮し、以下の物性値を有する標題化合物（７９９ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール：酢酸＝９０：１０：１）；
ＮＭＲ（CD₃OD）：δ4.05 (dd, J = 7.5, 4.2 Hz, 1H), 4.01 (dt, J = 4.2, 12.9 Hz, 1H), 3.59 (dt, J = 3.3, 12.9 Hz, 1H), 3.51 (m, 1H), 3.40 (brd, J = 5.4 Hz, 1H), 3.36 (brd, J = 5.4 Hz, 1H), 3.25 (m, 1H), 2.93 (s, 3H), 2.37 (dt, J = 5.4, 14.4 Hz, 1H), 2.32 (dt, J = 5.4, 14.4 Hz, 1H), 2.11 (brd, J = 14.4 Hz, 1H), 1.99 (brd, J = 14.4 Hz, 1H), 1.86-1.14 (m, 15H), 1.07-0.87 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H)。 Reference Example 6
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-4-methyl-1,4,9-triazaspiro [5.5] undecane hydrochloride

To a solution of the compound (1 g) produced in Reference Example 5 in methanol (20 ml) was added 10% palladium on carbon (60 mg). The reaction mixture was stirred at room temperature under a hydrogen gas atmosphere for 8 hours. The reaction mixture was filtered using Celite (trade name), and a 4N solution of hydrogen chloride in ethyl acetate was added to the filtrate, followed by concentration to obtain the title compound (799 mg) having the following physical data.
TLC: Rf 0.28 (chloroform: methanol: acetic acid = 90: 10: 1);
NMR (CD ₃ OD): δ 4.05 (dd, J = 7.5, 4.2 Hz, 1H), 4.01 (dt, J = 4.2, 12.9 Hz, 1H), 3.59 (dt, J = 3.3, 12.9 Hz, 1H) , 3.51 (m, 1H), 3.40 (brd, J = 5.4 Hz, 1H), 3.36 (brd, J = 5.4 Hz, 1H), 3.25 (m, 1H), 2.93 (s, 3H), 2.37 (dt, J = 5.4, 14.4 Hz, 1H), 2.32 (dt, J = 5.4, 14.4 Hz, 1H), 2.11 (brd, J = 14.4 Hz, 1H), 1.99 (brd, J = 14.4 Hz, 1H), 1.86- 1.14 (m, 15H), 1.07-0.87 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例６で製造した化合物を用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.32（酢酸エチル）；
ＮＭＲ（CD₃OD）：δ7.53 (d, J = 8.7 Hz, 2H), 7.39 (dd, J = 8.7, 7.5 Hz, 2H), 7.18 (t, J = 7.5 Hz, 1H), 7.09-7.01 (m, 4H), 4.34 (s, 2H), 4.05 (m, 1H), 4.04 (dd, J = 7.2, 3.9 Hz, 1H), 3.68-3.43 (m, 4H), 3.27 (m, 1H), 2.93 (s, 3H), 2.48 (dd, J = 14.4, 5.4 Hz, 1H), 2.39 (dd, J = 14.4, 5.4 Hz, 1H), 2.16 (brd, J = 14.4 Hz, 1H), 2.03 (brd, J = 14.4 Hz, 1H), 1.86-1.58 (m, 8H), 1.53-1.14 (m, 7H), 1.07-0.86 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H)。 Example 20
(3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-4-methyl-9- (4-phenyloxyphenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

Using the compound prepared in Reference Example 6 instead of the compound prepared in Reference Example 3, the same operation as in Example 2 was carried out to obtain the compound of the present invention having the following physical property values.
TLC: Rf 0.32 (ethyl acetate);
NMR (CD ₃ OD): δ 7.53 (d, J = 8.7 Hz, 2H), 7.39 (dd, J = 8.7, 7.5 Hz, 2H), 7.18 (t, J = 7.5 Hz, 1H), 7.09-7.01 (m, 4H), 4.34 (s, 2H), 4.05 (m, 1H), 4.04 (dd, J = 7.2, 3.9 Hz, 1H), 3.68-3.43 (m, 4H), 3.27 (m, 1H), 2.93 (s, 3H), 2.48 (dd, J = 14.4, 5.4 Hz, 1H), 2.39 (dd, J = 14.4, 5.4 Hz, 1H), 2.16 (brd, J = 14.4 Hz, 1H), 2.03 (brd , J = 14.4 Hz, 1H), 1.86-1.58 (m, 8H), 1.53-1.14 (m, 7H), 1.07-0.86 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（３）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（２−メチルプロパノイルアミノ）ベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.28 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.6 (s, 1H), 10.0 (s, 1H), 8.02 (m, 1H), 7.68 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8.7 Hz, 2H), 5.24 (s, 1H), 4.22 (s, 2H), 3.96 (m, 1H), 3.70 (m, 1H), 3.66-3.12 (m, 6H), 2.68-2.20 (m, 4H), 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 1.10 (d, J = 6.9 Hz, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 6.9 Hz, 3H)。 Example 21
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methylpropanoylamino) phenylmethyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (3) was replaced with 4- (2-methylpropanoylamino) benzoaldehyde in place of 3-formyl-6-phenyloxypyridine. The same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.6 (s, 1H), 10.0 (s, 1H), 8.02 (m, 1H), 7.68 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8.7) Hz, 2H), 5.24 (s, 1H), 4.22 (s, 2H), 3.96 (m, 1H), 3.70 (m, 1H), 3.66-3.12 (m, 6H), 2.68-2.20 (m, 4H) , 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 1.10 (d, J = 6.9 Hz, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 6.9 Hz, 3H ).

Examples 21 (1) to 21 (6)
The same operation as in Example 21 was performed using the corresponding aldehyde derivative instead of 4- (2-methylpropanoylamino) benzaldehyde, to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.36 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.5 (s, 1H), 9.95 (s, 1H), 8.02 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 4.26 (s, 2H), 4.02 (s, 2H), 3.96 (m, 1H), 3.80-3.10 (m, 7H), 3.38 (s, 3H), 2.60-2.18 (m, 4H), 2.02-1.44 (m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H)。 Example 21 (1)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methoxyacetylamino) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ10.5 (s, 1H), 9.95 (s, 1H), 8.02 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4) Hz, 2H), 4.26 (s, 2H), 4.02 (s, 2H), 3.96 (m, 1H), 3.80-3.10 (m, 7H), 3.38 (s, 3H), 2.60-2.18 (m, 4H) , 2.02-1.44 (m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.27 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.6 (s, 1H), 10.4 (s, 1H), 8.01 (m, 1H), 7.67 (d, J = 9.0 Hz, 2H), 7.54 (d, J = 9.0 Hz, 2H), 7.40-7.18 (m, 5H), 4.24 (s, 2H), 3.96 (s, 1H), 3.84-3.10 (m, 8H), 2.62-2.18 (m, 4H), 2.04-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H)。 Example 21 (2)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-phenylacetylamino) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.27 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.6 (s, 1H), 10.4 (s, 1H), 8.01 (m, 1H), 7.67 (d, J = 9.0 Hz, 2H), 7.54 (d, J = 9.0) Hz, 2H), 7.40-7.18 (m, 5H), 4.24 (s, 2H), 3.96 (s, 1H), 3.84-3.10 (m, 8H), 2.62-2.18 (m, 4H), 2.04-1.42 ( m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H).

ＴＬＣ：Ｒｆ 0.26 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.8 (s, 1H), 10.4 (s, 1H), 8.01 (m, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.37 (dd, J = 8.4, 5.4 Hz, 2H), 7.14 (t, J = 8.4 Hz, 2H), 4.34-3.10 (m, 8H), 4.24 (s, 2H), 3.96 (s, 1H), 2.66-2.18 (m, 4H), 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 6.9 Hz, 3H)。 Example 21 (3)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2- (4-fluorophenyl) acetylamino) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.26 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.8 (s, 1H), 10.4 (s, 1H), 8.01 (m, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4) Hz, 2H), 7.37 (dd, J = 8.4, 5.4 Hz, 2H), 7.14 (t, J = 8.4 Hz, 2H), 4.34-3.10 (m, 8H), 4.24 (s, 2H), 3.96 (s , 1H), 2.66-2.18 (m, 4H), 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.98-0.64 (m, 2H), 0.88 (t, J = 6.9 Hz, 3H ).

ＴＬＣ：Ｒｆ 0.35 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.90 (br.s, 1H), 10.70 (s, 1H), 8.05 (m, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.97 (s, 4H), 7.83 (d, J = 8.4 Hz, 2H), 5.24 (m, 1H), 4.43 (s, 2H), 3.97 (m, 1H), 3.90-3.06 (m, 7H), 3.84 (s, 3H), 2.62-2.20 (m, 3H), 2.06-1.42 (m, 8H), 1.40-1.02 (m, 6H), 0.98-0.66 (m, 2H), 0.89 (t, J = 6.9 Hz, 3H)。 Example 21 (4)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenylaminocarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.90 (br.s, 1H), 10.70 (s, 1H), 8.05 (m, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.97 (s, 4H) ), 7.83 (d, J = 8.4 Hz, 2H), 5.24 (m, 1H), 4.43 (s, 2H), 3.97 (m, 1H), 3.90-3.06 (m, 7H), 3.84 (s, 3H) , 2.62-2.20 (m, 3H), 2.06-1.42 (m, 8H), 1.40-1.02 (m, 6H), 0.98-0.66 (m, 2H), 0.89 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.41 (クロロホルム：メタノール＝１０：１)；
ＮＭＲ（d₆-DMSO）：δ10.6 (s, 1H), 8.03 (d, J = 8.7 Hz, 2H), 8.02 (m, 1H), 7.78 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 5.30 (s, 2H), 5.24 (m, 1H), 4.42 (s, 2H), 3.96 (m, 1H), 3.86-3.10 (m, 7H), 3.76 (s, 3H), 2.64-2.20 (m, 3H), 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.96-0.68 (m, 2H), 0.88 (t, J = 6.3 Hz, 3H)。 Example 21 (5)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethyloxycarbonyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.6 (s, 1H), 8.03 (d, J = 8.7 Hz, 2H), 8.02 (m, 1H), 7.78 (d, J = 8.7 Hz, 2H), 7.42 ( d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 5.30 (s, 2H), 5.24 (m, 1H), 4.42 (s, 2H), 3.96 (m, 1H), 3.86-3.10 (m, 7H), 3.76 (s, 3H), 2.64-2.20 (m, 3H), 2.02-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.96-0.68 (m, 2H ), 0.88 (t, J = 6.3 Hz, 3H).

ＴＬＣ：Ｒｆ 0.37 (クロロホルム：メタノール＝９：１)；
ＮＭＲ（CD₃OD）：δ8.35 (d, J = 2.5 Hz, 1H), 8.15 (dd, J = 8.5, 2.5 Hz, 1H), 7.89 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 1H), 4.39 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.75 (m, 1H), 3.57-3.45 (m, 3H), 3.30-3.22 (m, 2H), 2.92 (s, 3H), 2.56 (m, 1H), 2.50-2.39 (m, 2H), 2.14-1.91 (m, 3H), 1.80-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.00-0.87 (m, 2H), 0.95 (t, J = 7.0 Hz, 3H)。 Example 21 (6)
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (2- (4-methylaminocarbonylphenyloxy) pyridin-5-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.37 (chloroform: methanol = 9: 1);
NMR (CD ₃ OD): δ 8.35 (d, J = 2.5 Hz, 1H), 8.15 (dd, J = 8.5, 2.5 Hz, 1H), 7.89 (d, J = 8.5 Hz, 2H), 7.23 (d , J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 1H), 4.39 (s, 2H), 4.15 (d, J = 2.0 Hz, 1H), 4.00 (m, 1H), 3.75 (m , 1H), 3.57-3.45 (m, 3H), 3.30-3.22 (m, 2H), 2.92 (s, 3H), 2.56 (m, 1H), 2.50-2.39 (m, 2H), 2.14-1.91 (m , 3H), 1.80-1.60 (m, 5H), 1.50-1.10 (m, 6H), 1.00-0.87 (m, 2H), 0.95 (t, J = 7.0 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例３（９）で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−カルボキシフェニルオキシ）ベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.45（クロロホルム：メタノール＝５：１）；
ＮＭＲ（d₆-DMSO）：δ10.4 (s, 1H), 8.05 (m, 1H), 7.97 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 5.28 (d, J = 6.9 Hz, 1H) 4.35 (s, 2H), 3.97 (m, 1H), 3.88-3.12 (m, 7H), 2.64-2.20 (m, 3H), 2.06-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H), 0.80 (m, 2H)。 Example 22
(3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane hydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 3 (9) was replaced with 4- (4-carboxyphenyloxy) benzaldehyde in place of 3-formyl-6-phenyloxypyridine. The same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical data.
TLC: Rf 0.45 (chloroform: methanol = 5: 1);
NMR (d ₆ -DMSO): δ 10.4 (s, 1H), 8.05 (m, 1H), 7.97 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.19 ( d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7 Hz, 2H), 5.28 (d, J = 6.9 Hz, 1H) 4.35 (s, 2H), 3.97 (m, 1H), 3.88-3.12 (m, 7H), 2.64-2.20 (m, 3H), 2.06-1.42 (m, 8H), 1.40-1.00 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H), 0.80 (m, 2H ).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、Ｎ−ｔ−ブトキシカルボニル−３−ピリジル−Ｌ−アラニンを、Ｎ−ベンジル−４−ピペリドンの代わりに、Ｎ−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−４−ピペリドン、ベンジルイソニトリルの代わりに、２−モルホリノエチルイソニトリルを用いて、参考例１→参考例２→実施例１と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.25（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ8.82-8.76 (m, 2H), 8.55 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 7.8, 5.7 Hz, 1H), 7.84 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 7.15-7.02 (m, 4H), 4.55 (t, J = 5.4 Hz, 1H), 4.33 (s, 2H), 3.80 (m, 1H), 3.68-3.28 (m, 7H), 2.91 (s, 3H), 2.56-2.40 (m, 2H), 2.20 (m, 1H), 1.70 (m, 1H), 1.50-1.20 (m, 4H), 0.92 (t, J = 6.9 Hz, 3H)。 Example 23
(3S) -1-butyl-2,5-dioxo-3- (pyridin-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, Nt-butoxycarbonyl-3-pyridyl-L-alanine is replaced by N-benzyl-4. Reference Example 1 → Reference Example 2 using 2-morpholinoethyl isonitrile instead of N- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -4-piperidone and benzylisonitrile instead of -piperidone → The same operation as in Example 1 was performed to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.25 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 8.82-8.76 (m, 2H), 8.55 (d, J = 8.4 Hz, 1H), 8.06 (dd, J = 7.8, 5.7 Hz, 1H), 7.84 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 7.15-7.02 (m, 4H), 4.55 (t, J = 5.4 Hz, 1H), 4.33 (s, 2H), 3.80 (m, 1H), 3.68-3.28 (m, 7H), 2.91 (s, 3H), 2.56-2.40 (m, 2H), 2.20 (m, 1H), 1.70 (m, 1H), 1.50-1.20 (m, 4H) , 0.92 (t, J = 6.9 Hz, 3H).

Examples 23 (1) to 23 (5)
The same operation as in Example 23 was carried out using the corresponding amino acid derivative instead of Nt-butoxycarbonyl-3-pyridyl-L-alanine, to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.51 (クロロホルム：メタノール：酢酸＝２０：２：１)；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.56 (d, J = 9.0 Hz, 2H), 7.30-7.04 (m, 9H), 4.36 (dd, J = 4.5, 3.6 Hz, 1H), 4.25 (s, 2H), 3.78 (m, 1H), 3.50-3.02 (m, 6H), 3.00-2.84 (m, 4H), 2.38 (m, 1H), 2.02 (m, 1H), 1.86 (m, 1H), 1.60-1.24 (m, 4H), 0.93 (t, J = 6.9 Hz, 3H), 0.04 (m, 1H)。 Example 23 (1)
(3S) -1-butyl-2,5-dioxo-3-phenylmethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.51 (chloroform: methanol: acetic acid = 20: 2: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.56 (d, J = 9.0 Hz, 2H), 7.30-7.04 (m, 9H), 4.36 (dd, J = 4.5, 3.6 Hz, 1H), 4.25 (s, 2H), 3.78 (m, 1H), 3.50-3.02 (m, 6H), 3.00-2.84 (m, 4H), 2.38 (m, 1H), 2.02 (m, 1H) ), 1.86 (m, 1H), 1.60-1.24 (m, 4H), 0.93 (t, J = 6.9 Hz, 3H), 0.04 (m, 1H).

ＴＬＣ：Ｒｆ 0.46 (クロロホルム：メタノール：酢酸＝２０：２：１)；
ＮＭＲ（CD₃OD）：δ8.78 (dd, J = 7.5, 1.5 Hz, 1H), 8.57 (td, J = 7.8, 1.5 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 8.00 (m, 1H), 7.84 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 6.6 Hz, 2H), 7.16-7.04 (m, 4H), 4.68 (dd, J = 6.9, 5.7 Hz, 1H), 4.38 (s, 2H), 3.84 (m, 1H), 3.70-3.32 (m, 7H), 2.91 (s, 3H), 2.64-2.44 (m, 2H), 2.16 (m, 1H), 2.06 (m, 1H), 1.50-1.22 (m, 4H), 0.91 (t, J = 6.9 Hz, 3H)。 Example 23 (2)
(3S) -1-butyl-2,5-dioxo-3- (pyridin-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane dihydrochloride

TLC: Rf 0.46 (chloroform: methanol: acetic acid = 20: 2: 1);
NMR (CD ₃ OD): δ 8.78 (dd, J = 7.5, 1.5 Hz, 1H), 8.57 (td, J = 7.8, 1.5 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 8.00 (m, 1H), 7.84 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 6.6 Hz, 2H), 7.16-7.04 (m, 4H), 4.68 (dd, J = 6.9, 5.7 Hz, 1H), 4.38 (s, 2H), 3.84 (m, 1H), 3.70-3.32 (m, 7H), 2.91 (s, 3H), 2.64-2.44 (m, 2H), 2.16 (m, 1H), 2.06 (m, 1H), 1.50-1.22 (m, 4H), 0.91 (t, J = 6.9 Hz, 3H).

ＴＬＣ：Ｒｆ 0.28 (クロロホルム：メタノール：酢酸＝２０：２：１)；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.02-3.88 (m, 3H), 3.80-3.44 (m, 5H), 3.30 (m, 1H), 2.91 (s, 3H), 2.60-2.36 (m, 3H), 2.18 (m, 1H), 1.64 (m, 1H), 1.50-1.26 (m, 3H), 1.02-0.90 (m, 3H)。 Example 23 (3)
(3S) -1-butyl-2,5-dioxo-3-hydroxymethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane・ Hydrochloride

TLC: Rf 0.28 (chloroform: methanol: acetic acid = 20: 2: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.36 (s, 2H), 4.02-3.88 (m, 3H), 3.80-3.44 (m, 5H), 3.30 (m, 1H), 2.91 (s, 3H), 2.60-2.36 ( m, 3H), 2.18 (m, 1H), 1.64 (m, 1H), 1.50-1.26 (m, 3H), 1.02-0.90 (m, 3H).

ＴＬＣ：Ｒｆ 0.86 (クロロホルム：メタノール：酢酸＝１０：２：１)；
ＮＭＲ（CD₃OD）：δ8.70 (dd, J = 5.4, 1.0 Hz, 1H), 8.05 (td, J = 6.6, 1.2 Hz, 1H), 7.92-7.72 (m, 4H), 7.64 (d, J = 9.0 Hz, 2H), 7.20-7.06 (m, 4H), 4.67 (d, J = 6.3 Hz, 1H), 4.36 (s, 2H), 3.86-3.18 (m, 8H), 2.91 (s, 3H), 2.70-2.26 (m, 2H), 2.34-2.06 (m, 2H), 1.60-1.44 (m, 2H), 1.44-1.24 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H)。 Example 23 (4)
(3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.86 (chloroform: methanol: acetic acid = 10: 2: 1);
NMR (CD ₃ OD): δ 8.70 (dd, J = 5.4, 1.0 Hz, 1H), 8.05 (td, J = 6.6, 1.2 Hz, 1H), 7.92-7.72 (m, 4H), 7.64 (d, J = 9.0 Hz, 2H), 7.20-7.06 (m, 4H), 4.67 (d, J = 6.3 Hz, 1H), 4.36 (s, 2H), 3.86-3.18 (m, 8H), 2.91 (s, 3H ), 2.70-2.26 (m, 2H), 2.34-2.06 (m, 2H), 1.60-1.44 (m, 2H), 1.44-1.24 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H).

ＴＬＣ：Ｒｆ 0.65 (クロロホルム：メタノール：酢酸＝１０：２：１)；
ＮＭＲ（CD₃OD）：δ8.74-8.60 (m, 2H), 8.06 (d, J = 7.8 Hz, 1H), 7.88 (m, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.12 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.52 (t, J = 5.1 Hz, 1H), 4.33 (s, 2H), 4.00 (m, 1H), 3.78 (m, 1H), 3.60 (m, 1H), 3.56-3.18 (m, 5H), 2.91 (s, 3H), 2.56-2.18 (m, 2H), 2.20 (m, 1H), 1.66 (m, 1H), 1.52-1.22 (m, 4H), 0.93 (t, J = 6.9 Hz, 3H)。 Example 23 (5)
(3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4 9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.65 (chloroform: methanol: acetic acid = 10: 2: 1);
NMR (CD ₃ OD): δ 8.74-8.60 (m, 2H), 8.06 (d, J = 7.8 Hz, 1H), 7.88 (m, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.12 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.52 (t, J = 5.1 Hz, 1H), 4.33 (s , 2H), 4.00 (m, 1H), 3.78 (m, 1H), 3.60 (m, 1H), 3.56-3.18 (m, 5H), 2.91 (s, 3H), 2.56-2.18 (m, 2H), 2.20 (m, 1H), 1.66 (m, 1H), 1.52-1.22 (m, 4H), 0.93 (t, J = 6.9 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシル−３−ヒドロキシプロパン酸を、ｎ−ブチルアミンの代わりに、４−メトキシベンジルアミンを、Ｎ−ベンジル−４−ピペリドンの代わりに、Ｎ−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニルメチル）−４−ピペリドン、ベンジルイソニトリルの代わりに、２−モルホリノエチルイソニトリルを用いて、参考例１→参考例２→実施例１と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.24（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.48 (m, 1H), 4.33 (s, 4H), 3.96 (m, 1H), 3.75 (m, 1H), 3.75 (s, 3H), 3.58-3.18 (m, 3H), 2.92 (s, 3H), 2.66-2.28 (m, 3H), 2.16-1.58 (m, 7H), 1.40-0.82 (m, 5H)。 Example 24
(3R) -1- (4-methoxyphenylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, (2R, 3R) -2- (t-butoxycarbonylamino) -3-cyclohexyl-3 -Hydroxypropanoic acid, 4-methoxybenzylamine in place of n-butylamine and N- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -4 in place of N-benzyl-4-piperidone -Reference Example 1 → Reference Example 2 → The same operation as in Example 1 was performed using 2-morpholinoethyl isonitrile instead of piperidone and benzyl isonitrile to obtain the compound of the present invention having the following physical data.
TLC: Rf 0.24 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.48 (m, 1H), 4.33 (s, 4H), 3.96 (m, 1H ), 3.75 (m, 1H), 3.75 (s, 3H), 3.58-3.18 (m, 3H), 2.92 (s, 3H), 2.66-2.28 (m, 3H), 2.16-1.58 (m, 7H), 1.40-0.82 (m, 5H).

Examples 24 (1) to 24 (4)
The same operation as in Example 24 was carried out using the corresponding amine instead of 4-methoxybenzylamine, to obtain the present compound shown below.

ＴＬＣ：Ｒｆ 0.28（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.85 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.40-7.02 (m, 5H), 7.13 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.58 (m, 1H), 4.33 (s, 4H), 3.96 (m, 1H), 3.76 (m, 1H), 3.54-3.18 (m, 3H), 2.92 (s, 3H), 2.64-2.28 (m, 3H), 2.14-1.58 (m, 7H), 1.40-0.80 (m, 5H)。 Example 24 (1)
(3R) -1-phenylmethyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl)- 1,4,9-Triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.28 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.85 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.40-7.02 (m, 5H), 7.13 (d, J = 8.7 Hz) , 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.58 (m, 1H), 4.33 (s, 4H), 3.96 (m, 1H), 3.76 (m, 1H), 3.54-3.18 (m, 3H), 2.92 (s, 3H), 2.64-2.28 (m, 3H), 2.14-1.58 (m, 7H), 1.40-0.80 (m, 5H).

ＴＬＣ：Ｒｆ 0.35（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.18 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.86-3.18 (m, 8H), 3.31 (s, 3H), 2.91 (s, 3H), 2.60-1.58 (m, 10H), 1.42-0.80 (m, 5H)。 Example 24 (2)
(3R) -1- (2-methoxyethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride

TLC: Rf 0.35 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 8.7 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.18 (d, J = 2.1 Hz, 1H), 3.98 (m, 1H), 3.86-3.18 (m, 8H), 3.31 (s, 3H), 2.91 (s, 3H), 2.60-1.58 (m, 10H), 1.42-0.80 (m, 5H).

ＴＬＣ：Ｒｆ 0.83（クロロホルム：メタノール：酢酸＝１０：２：１）；
ＮＭＲ（CD₃OD）：δ8.76 (dd, J = 6.6, 1.8 Hz, 1H), 8.54 (td, J = 8.4, 1.8 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.93 (dd, J = 8.4, 6.6 Hz, 1H), 7.83 (d, J = 9.0 Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.14-7.02 (m, 4H), 5.34-5.20 (m, 2H), 4.38 (s, 2H), 4.30 (d, J = 1.8 Hz, 1H), 3.96 (m, 1H), 3.78 (m, 1H), 3.52-3.38 (m, 2H), 3.32 (m, 1H), 2.90 (s, 3H), 2.72-2.54 (m, 3H), 2.30 (m, 1H), 2.06 (m, 1H), 1.88 (m, 1H), 1.82-1.50 (m, 4H), 1.28-1.06 (m, 3H), 1.06-0.80 (m, 2H)。 Example 24 (3)
(3R) -1- (pyridin-2-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.83 (chloroform: methanol: acetic acid = 10: 2: 1);
NMR (CD ₃ OD): δ 8.76 (dd, J = 6.6, 1.8 Hz, 1H), 8.54 (td, J = 8.4, 1.8 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.93 (dd, J = 8.4, 6.6 Hz, 1H), 7.83 (d, J = 9.0 Hz, 2H), 7.65 (d, J = 8.7 Hz, 2H), 7.14-7.02 (m, 4H), 5.34-5.20 ( m, 2H), 4.38 (s, 2H), 4.30 (d, J = 1.8 Hz, 1H), 3.96 (m, 1H), 3.78 (m, 1H), 3.52-3.38 (m, 2H), 3.32 (m , 1H), 2.90 (s, 3H), 2.72-2.54 (m, 3H), 2.30 (m, 1H), 2.06 (m, 1H), 1.88 (m, 1H), 1.82-1.50 (m, 4H), 1.28-1.06 (m, 3H), 1.06-0.80 (m, 2H).

ＴＬＣ：Ｒｆ 0.58（クロロホルム：メタノール：酢酸＝１０：２：１）；
ＮＭＲ（CD₃OD）：δ8.89 (s, 1H), 8.73 (d, J = 5.7 Hz, 1H), 8.64 (d, J = 8.1 Hz, 1H), 8.03 (dd, J = 8.1, 5.7 Hz, 1H), 7.83 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.18-7.02 (m, 4H), 5.19 (d, J = 18.0 Hz, 1H), 5.11 (d, J = 18.0 Hz, 1H), 4.40-4.26 (m, 3H), 3.90 (m, 1H), 3.78 (m, 1H), 3.50-3.38 (m, 2H), 3.30 (m, 1H), 2.90 (s, 3H), 2.74-2.42 (m, 3H), 2.20-1.88 (m, 3H), 1.82-1.56 (m, 4H), 1.32-1.06 (m, 3H), 1.02-0.80 (m, 2H)。 Example 24 (4)
(3R) -1- (pyridin-3-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane dihydrochloride

TLC: Rf 0.58 (chloroform: methanol: acetic acid = 10: 2: 1);
NMR (CD ₃ OD): δ 8.89 (s, 1H), 8.73 (d, J = 5.7 Hz, 1H), 8.64 (d, J = 8.1 Hz, 1H), 8.03 (dd, J = 8.1, 5.7 Hz) , 1H), 7.83 (d, J = 8.7 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.18-7.02 (m, 4H), 5.19 (d, J = 18.0 Hz, 1H), 5.11 (d, J = 18.0 Hz, 1H), 4.40-4.26 (m, 3H), 3.90 (m, 1H), 3.78 (m, 1H), 3.50-3.38 (m, 2H), 3.30 (m, 1H), 2.90 (s, 3H), 2.74-2.42 (m, 3H), 2.20-1.88 (m, 3H), 1.82-1.56 (m, 4H), 1.32-1.06 (m, 3H), 1.02-0.80 (m, 2H ).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、Ｎ−ｔ−ブトキシカルボニル−Ｄ−シクロヘキシルアラニンを用いて、参考例１→参考例２→実施例１→参考例３と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.59（ｎ−ブタノール：酢酸：水＝４：２：１）；
ＮＭＲ（CD₃OD）：δ4.05 (dd, J = 7.5, 4.8 Hz, 1H), 3.83-3.69 (m, 2H), 3.42-3.37 (m, 4H), 2.39-2.07 (m, 4H), 1.80-1.49 (m, 10H), 1.45-1.19 (m, 5H), 1.03-0.91 (m, 5H)；
比旋光度：［α］_D +35.5 （c 1.05、メタノール、21℃）。 Reference Example 7
(3R) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-triazaspiro [5.5] undecane hydrochloride

Reference example 1 → Reference example using Nt-butoxycarbonyl-D-cyclohexylalanine instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid 2 → Example 1 → The same operation as in Reference Example 3 was carried out to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.59 (n-butanol: acetic acid: water = 4: 2: 1);
NMR (CD ₃ OD): δ 4.05 (dd, J = 7.5, 4.8 Hz, 1H), 3.83-3.69 (m, 2H), 3.42-3.37 (m, 4H), 2.39-2.07 (m, 4H), 1.80-1.49 (m, 10H), 1.45-1.19 (m, 5H), 1.03-0.91 (m, 5H);
Specific rotation: [α] _D +35.5 (c 1.05, methanol, 21 ° C.).

参考例３で製造した化合物の代わりに、参考例７で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−カルボキシフェニルオキシ）ベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.36（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（d₆-DMSO）：δ10.92 (br-s, 1H), 8.41 (br-s, 1H), 7.95 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 3.91 (m, 1H), 3.59-3.35 (m, 6H), 2.56-2.35 (m, 2H), 2.10 (m, 1H), 1.98 (m, 1H), 1.72-1.35 (m, 10H), 1.32-1.14 (m, 5H), 0.90-0.78 (m, 5H)。 Example 25
(3R) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane / hydrochloric acid salt

The compound prepared in Reference Example 7 was replaced with the compound prepared in Reference Example 7 using 4- (4-carboxyphenyloxy) benzaldehyde instead of 3-formyl-6-phenyloxypyridine. The same operation as in Example 2 was performed to obtain the compound of the present invention having the following physical data.
TLC: Rf 0.36 (chloroform: methanol = 10: 1);
NMR (d ₆ -DMSO): δ 10.92 (br-s, 1H), 8.41 (br-s, 1H), 7.95 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H) ), 7.17 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.32 (s, 2H), 3.91 (m, 1H), 3.59-3.35 (m, 6H), 2.56 -2.35 (m, 2H), 2.10 (m, 1H), 1.98 (m, 1H), 1.72-1.35 (m, 10H), 1.32-1.14 (m, 5H), 0.90-0.78 (m, 5H).

実施例２３（２）で製造した化合物のフリー体（１１７ｍｇ）のクロロホルム（１０ｍｌ）溶液に、室温にて３−クロロ過安息香酸（１１４ｍｇ）のクロロホルム（４ｍｌ）溶液を滴下した。反応混合物を室温で一晩撹拌した後溶媒を留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（富士シリシア社、ＮＨ−ＤＭ１０２０、クロロホルム）によって精製し、以下の物性値を有する本発明化合物（１００ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.23（クロロホルム：メタノール：酢酸＝２０：２：１）；
ＮＭＲ（CDCl₃）：δ8.81 (s, 1H), 8.28 (dd, J = 6.0, 1.2 Hz, 1H), 7.77 (d, J = 8.7 Hz, 2H), 7.52-7.46 (m, 3H), 7.32-7.22 (m, 2H), 7.16-6.98 (m, 4H), 6.32 (m, 1H), 4.40-4.24 (m, 4H), 3.87 (dd, J = 11.0, 5.1 Hz, 1H), 3.66-3.34 (m, 4H), 3.16-2.86 (m, 4H), 3.01 (d, J = 4.5 Hz, 3H), 1.84-1.20 (m, 6H), 0.90 (t, J = 7.2 Hz, 3H)。 Example 26
(3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane-9-oxide

A chloroform (4 ml) solution of 3-chloroperbenzoic acid (114 mg) was added dropwise to a chloroform (10 ml) solution of the free compound (117 mg) of the compound produced in Example 23 (2) at room temperature. After stirring the reaction mixture at room temperature overnight, the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (Fuji Silysia, NH-DM1020, chloroform) to give the compound of the present invention (100 mg) having the following physical data.
TLC: Rf 0.23 (chloroform: methanol: acetic acid = 20: 2: 1);
NMR (CDCl ₃ ): δ 8.81 (s, 1H), 8.28 (dd, J = 6.0, 1.2 Hz, 1H), 7.77 (d, J = 8.7 Hz, 2H), 7.52-7.46 (m, 3H), 7.32-7.22 (m, 2H), 7.16-6.98 (m, 4H), 6.32 (m, 1H), 4.40-4.24 (m, 4H), 3.87 (dd, J = 11.0, 5.1 Hz, 1H), 3.66- 3.34 (m, 4H), 3.16-2.86 (m, 4H), 3.01 (d, J = 4.5 Hz, 3H), 1.84-1.20 (m, 6H), 0.90 (t, J = 7.2 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、２−（ｔ−ブトキシカルボニルアミノ）−３−（モルホリン−４−イル）プロパン酸を用いて、参考例１→参考例２→実施例１→参考例３と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.07（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ4.76 (dd, J = 8.4, 4.8 Hz, 1H), 4.05-3.82 (m, 6H), 3.71-3.40 (m, 10H), 2.41 (m, 1H), 2.31-2.21 (m, 3H), 1.98-1.54 (m, 2H), 1.46-1.36 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H)。 Reference Example 8
1-butyl-2,5-dioxo-3- (morpholin-4-ylmethyl) 1,4,9-triazaspiro [5.5] undecane dihydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, 2- (t-butoxycarbonylamino) -3- (morpholin-4-yl) propanoic acid And the same operation as in Reference Example 1 → Reference Example 2 → Example 1 → Reference Example 3 was carried out to obtain a compound of the present invention having the following physical properties.
TLC: Rf 0.07 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 4.76 (dd, J = 8.4, 4.8 Hz, 1H), 4.05-3.82 (m, 6H), 3.71-3.40 (m, 10H), 2.41 (m, 1H), 2.31- 2.21 (m, 3H), 1.98-1.54 (m, 2H), 1.46-1.36 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H).

参考例３で製造した化合物の代わりに、参考例８で製造した化合物を、３−ホルミル−６−フェニルオキシピリジンの代わりに、４−（４−メチルアミノカルボニル）フェニルオキシベンゾアルデヒドを用いて、実施例２と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.41（クロロホルム：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.73 (dd, J = 8.1, 5.1 Hz, 1H), 4.37 (s, 2H), 4.10-3.85 (m, 5H), 3.76-3.43 (m, 9H), 3.40-3.20 (m, 2H), 2.91 (s, 3H), 2.63-2.43 (m, 2H), 2.33-2.24 (m, 2H), 1.65-1.50 (m, 2H), 1.44-1.34 (m, 2H), 0.96 (t, J = 7.0 Hz, 3H)。 Example 27
1-butyl-2,5-dioxo-3- (morpholin-4-ylmethyl) 9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane .Dihydrochloride

Instead of the compound prepared in Reference Example 3, the compound prepared in Reference Example 8 was replaced with 4- (4-methylaminocarbonyl) phenyloxybenzoaldehyde in place of 3-formyl-6-phenyloxypyridine, The same operation as in Example 2 was carried out to obtain the compound of the present invention having the following physical properties.
TLC: Rf 0.41 (chloroform: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 4.73 (dd, J = 8.1, 5.1 Hz, 1H), 4.37 (s, 2H), 4.10-3.85 (m, 5H), 3.76-3.43 (m, 9H), 3.40-3.20 ( m, 2H), 2.91 (s, 3H), 2.63-2.43 (m, 2H), 2.33-2.24 (m, 2H), 1.65-1.50 (m, 2H), 1.44-1.34 (m, 2H), 0.96 ( t, J = 7.0 Hz, 3H).

実施例９（５４）で製造した化合物（１２０ｍｇ）と（１−メトキシ−イソプロピル）オキシアミン（３１ｍｇ）のジメチルホルムアミド（1.6ｍｌ）懸濁液に、ジイソプロピルエチルアミン（６８μｌ）、１−エチル−３−［３−（ジメチルアミノ）プロピル］カルボジイミド・塩酸塩（５６ｍｇ）、１−ヒドロキシベンズトリアゾール（４０ｍｇ）を加えた。反応混合物を室温で１時間撹拌した。反応混合物に、１Ｎ塩酸（２ｍｌ）を加え、室温にて１５分間撹拌した。反応混合物を水で希釈し、酢酸エチルで抽出した。抽出物を水、飽和炭酸水素ナトリウム水溶液、飽和塩化ナトリウム水溶液にて洗浄し、無水硫酸ナトリウムで乾燥し、濃縮した。得られた残渣のメタノール溶液に、４Ｎ塩化水素酢酸エチル溶液を加え、濃縮した。得られた残渣を酢酸エチルで洗浄し、以下の物性値を有する標題化合物（１１６ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.43（クロロホルム：メタノール：酢酸＝２０：４：１）；
ＮＭＲ（CD₃OD）：δ7.79 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.75 (m, 1H), 3.60-3.40 (m, 3H), 3.30-3.11 (m, 2H), 2.58-2.27 (m, 3H), 2.19-1.96 (m, 3H), 1.93-1.60 (m, 5H), 1.50-1.09 (m, 6H), 1.05-0.80 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H)。 Example 28
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (N-hydroxycarbamoyl) phenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane hydrochloride

In a suspension of the compound (120 mg) produced in Example 9 (54) and (1-methoxy-isopropyl) oxyamine (31 mg) in dimethylformamide (1.6 ml), diisopropylethylamine (68 μl) and 1-ethyl-3- [ 3- (Dimethylamino) propyl] carbodiimide.hydrochloride (56 mg) and 1-hydroxybenztriazole (40 mg) were added. The reaction mixture was stirred at room temperature for 1 hour. 1N hydrochloric acid (2 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. To a methanol solution of the obtained residue was added a 4N solution of hydrogen chloride in ethyl acetate, and the mixture was concentrated. The obtained residue was washed with ethyl acetate to give the title compound (116 mg) having the following physical data.
TLC: Rf 0.43 (chloroform: methanol: acetic acid = 20: 4: 1);
NMR (CD ₃ OD): δ 7.79 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 4.36 (s, 2H), 4.15 (d, J = 2.1 Hz, 1H), 4.00 (m, 1H), 3.75 (m, 1H), 3.60-3.40 (m, 3H), 3.30 -3.11 (m, 2H), 2.58-2.27 (m, 3H), 2.19-1.96 (m, 3H), 1.93-1.60 (m, 5H), 1.50-1.09 (m, 6H), 1.05-0.80 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H).

４−（４−メチルアミノカルボニルフェニルオキシ）安息香酸（53.8ｍｇ）のジメチルホルムアミド（４ｍｌ）溶液に、１−ヒドロキシベンズトリアゾール（34.9ｍｇ）と１−エチル−３−［３−（ジメチルアミノ）プロピル］カルボジイミド・塩酸塩（49.5ｍｇ）を加えた。反応混合物を室温で４０分間撹拌した。反応混合物に実施例３（３）で製造した化合物（１００ｍｇ）を加え、室温で１９時間撹拌した。反応混合物を塩化メチレンで希釈し、水を加え、塩化メチレンで抽出した。抽出物を１０％クエン酸水溶液と飽和塩化ナトリウム水溶液で洗浄し、無水硫酸ナトリウムで乾燥し、濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（酢酸エチル：メタノール＝１０：１）によって精製し、エーテルで洗浄し、以下の物性値を有する標題化合物（56.1ｍｇ）を得た。
ＴＬＣ：Ｒｆ 0.41（酢酸エチル：メタノール＝１０：１）；
ＮＭＲ（CD₃OD）：δ7.84 (d, J = 8.7 Hz, 2H), 7.49 (t, J = 8.7 Hz, 2H), 7.13-7.06 (m, 4H), 3.70 (m, 1H), 4.16 (m, 1H), 4.12-2.98 (m, 6H), 2.91 (s, 3H), 2.42-0.80 (m, 19H), 0.96 (t, J = 6.9 Hz, 3H)。 Example 29
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylcarbonyl) -1 , 4,9-Triazaspiro [5.5] undecane

In a solution of 4- (4-methylaminocarbonylphenyloxy) benzoic acid (53.8 mg) in dimethylformamide (4 ml), 1-hydroxybenztriazole (34.9 mg) and 1-ethyl-3- [3- (dimethylamino) propyl ] Carbodiimide hydrochloride (49.5 mg) was added. The reaction mixture was stirred at room temperature for 40 minutes. The compound (100 mg) produced in Example 3 (3) was added to the reaction mixture, and the mixture was stirred at room temperature for 19 hours. The reaction mixture was diluted with methylene chloride, water was added, and extracted with methylene chloride. The extract was washed with a 10% aqueous citric acid solution and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate: methanol = 10: 1), and washed with ether to give the title compound (56.1 mg) having the following physical data.
TLC: Rf 0.41 (ethyl acetate: methanol = 10: 1);
NMR (CD ₃ OD): δ 7.84 (d, J = 8.7 Hz, 2H), 7.49 (t, J = 8.7 Hz, 2H), 7.13-7.06 (m, 4H), 3.70 (m, 1H), 4.16 (m, 1H), 4.12-2.98 (m, 6H), 2.91 (s, 3H), 2.42-0.80 (m, 19H), 0.96 (t, J = 6.9 Hz, 3H).

（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−ヒドロキシ−４−メチルペンタン酸の代わりに、（２Ｒ，３Ｒ）−２−（ｔ−ブトキシカルボニルアミノ）−３−シクロヘキシル−３−ヒドロキシプロパン酸を、Ｎ−ベンジル−４−ピペリドンの代わりに、Ｎ−（４−（４−メチルアミノカルボニルフェニルオキシ）フェニル）−４−ピペリドン、ベンジルイソニトリルの代わりに、２−モルホリノエチルイソニトリルを用いて、参考例１→参考例２→実施例１と同様の操作をし、以下の物性値を有する本発明化合物を得た。
ＴＬＣ：Ｒｆ 0.40（酢酸エチル）；
ＮＭＲ（CD₃OD）：δ7.87 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 7.25 (d, J = 9.0 Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H), 4.65 (m, 1H), 4.39 (m, 1H), 4.20 (d, J = 1.8 Hz, 1H), 3.73-3.65 (m, 3H), 3.43-3.27 (m, 2H), 2.91 (s, 3H), 2.90-2.52 (m, 3H), 2.25 (m, 1H), 2.10-1.90 (m, 2H), 1.85-1.60 (m, 5H), 1.60-1.10 (m, 6H), 0.99 (t, J = 7.2 Hz, 3H), 1.00-0.82 (m, 2H)。 Example 30
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenyl) -1, 4,9-Triazaspiro [5.5] undecane hydrochloride

Instead of (2R, 3R) -2- (t-butoxycarbonylamino) -3-hydroxy-4-methylpentanoic acid, (2R, 3R) -2- (t-butoxycarbonylamino) -3-cyclohexyl-3 N- (4- (4-methylaminocarbonylphenyloxy) phenyl) -4-piperidone instead of N-benzyl-4-piperidone, 2-morpholinoethyl isonitrile instead of benzylisonitrile Reference Example 1 → Reference Example 2 → Example 1 was used to obtain a compound of the present invention having the following physical properties.
TLC: Rf 0.40 (ethyl acetate);
NMR (CD ₃ OD): δ 7.87 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 7.25 (d, J = 9.0 Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H), 4.65 (m, 1H), 4.39 (m, 1H), 4.20 (d, J = 1.8 Hz, 1H), 3.73-3.65 (m, 3H), 3.43-3.27 (m, 2H) , 2.91 (s, 3H), 2.90-2.52 (m, 3H), 2.25 (m, 1H), 2.10-1.90 (m, 2H), 1.85-1.60 (m, 5H), 1.60-1.10 (m, 6H) , 0.99 (t, J = 7.2 Hz, 3H), 1.00-0.82 (m, 2H).

Formulation Example 1
The following components were mixed by a conventional method and then tableted to obtain 100 tablets each containing 50 mg of the active ingredient.
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1,4, 9-triazaspiro [5.5] undecane dihydrochloride 5.0 g
・ Carboxymethylcellulose calcium (disintegrant) ・ ・ ・ ・ ・ ・ ・ 0.2g
・ Magnesium stearate (lubricant) 0.1 g
・ Microcrystalline cellulose ・ ・ ・ ・ ・ 4.7g

Formulation Example 2
After the following components were mixed by a conventional method, the solution was sterilized by a conventional method, filled into ampoules of 5 ml each, and freeze-dried by a conventional method to obtain 100 ampoules containing 20 mg of the active ingredient in one ampule. .
(3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1,4 9-triazaspiro [5.5] undecane dihydrochloride 2.0 g
・ Mannitol 20g
・ Distilled water ・ ・ ・ ・ 500ml

Claims (9)

General formula (I)

[Wherein, R ¹ is a group represented by the following formula (1) or (2):

(In the group, G represents a single bond, a C1-4 alkylene group, a C2-4 alkenylene group, or -CO-,
Ring A is (1) a C5-10 monocyclic or bicyclic carbocyclic ring, or (2) a 5-10 membered monocyclic ring containing 1-2 nitrogen atoms and / or 1-2 oxygen atoms. Or represents a bicyclic heterocycle,
R ⁶ is
(1) a C1-4 alkyl group,
(2) a halogen atom,
(3) a nitrile group,
(4) trifluoromethyl group,
(5) -OR ⁸ groups,
(6) -SR ⁹ groups,
(7) —NR ¹⁰ R ¹¹ groups,
(8) -COOR ¹² groups,
(9) —CONR ¹³ R ¹⁴ groups,
(10) —SO ₂ NR ¹⁵ R ¹⁶ groups,
(11) —NR ¹⁷ SO ₂ R ¹⁸ groups,
(12) —S (O) R ¹⁹ groups,
(13) —SO ₂ R ²⁰ groups,
(14) —N (SO ₂ R ²¹ ) ₂ groups,
(15) (a) -OR ⁸ group, (b) -NR ¹⁰ R ¹¹ group and (c) C1 -4 alkyl group substituted by one group selected from Cyc1 or (16) -NR ^27, Represents a COR ²⁸ group,
R ⁸ to R ¹⁷ are each independently (1) hydrogen atom, (2) C1 -4 alkyl group, (3) Cyc1, (4) -OR ²² group, or (5) (a) -OR ²² or represents radicals, the (b) -NR ²³ R ²⁴ groups, C1 -4 alkyl group substituted with one group selected arbitrarily from (c) -COOR ²⁵ radical and (d) Cyc1,
R ¹⁰ and R ¹¹ , R ¹³ and R ¹⁴ , R ¹⁵ and R ¹⁶ together with the nitrogen atom to which they are attached, contain 1 to 2 nitrogen atoms and / or 1 oxygen atom Represents a 6-membered monocyclic heterocycle (provided that the heterocycle may be substituted with a C1-4 alkyl group or a hydroxyl group);
R ^{22 to} R ²⁵ each independently represent (1) a hydrogen atom, (2) a C1-4 alkyl group, or (3) a C1-4 alkyl group substituted with a C1-4 alkoxy group,
R ²³ and R ²⁴ together with the bonding nitrogen atom represent a 5- to 6-membered monocyclic heterocyclic ring containing 1 to 2 nitrogen atoms and / or 1 oxygen atom (provided that the heterocyclic The ring may be substituted with a C1-4 alkyl group or a hydroxyl group.),
R ¹⁸ to R ²¹ each independently represent a C1~4 alkyl group,
R ²⁷ is (1) hydrogen atom, (2) C1 -4 alkyl group, (3) Cyc1, or (4) (a) -OR ²² group, (b) -NR ²³ R ²⁴ group, (c) -COOR ^A C1-4 alkyl group substituted by ²⁵ groups and one group arbitrarily selected from (d) Cyc1,
R ²⁸ is, (1) C1 -4 alkyl group, (2) Cyc1 or (3) (a) -OR ²² group, (b) -NR ²³ R ²⁴ group, (c) -COOR ²⁵ radical and (d) A C1-4 alkyl group substituted by one group arbitrarily selected from Cyc1,
Cyc1 represents (1) a C5-6 monocyclic carbocycle or (2) a 5- to 6-membered monocyclic heterocyclic ring containing 1-2 nitrogen atoms and / or one oxygen atom (provided that the carbon ring or heterocyclic ring, C1 -4 alkoxy group, a halogen atom or -COOR ²⁹ group (R ²⁹ is (1) hydrogen atom, (2) C1 -4 alkyl group, (3) Cyc1, or (4) (a) -OR ²² groups, substituted by (b) -NR ²³ R ²⁴ group represents a C1~4 alkyl group substituted by one group selected arbitrarily from (c) -COOR ²⁵ radical and (d) Cyc1.) May be done.),
E represents a single bond, -O-, -S-, -CO-, or -CHOH-,
Ring B represents (1) a C5-6 monocyclic carbocyclic ring or (2) a 5- to 6-membered monocyclic heterocyclic ring containing 1-2 nitrogen atoms and / or one oxygen atom,
R ⁷ represents a C1-4 alkyl group or a halogen atom,
n represents 0 or an integer of 1 to 4,
m represents 0 or an integer of 1 to 4. )
R ² is
(1) a C1-4 alkyl group,
(2) C2-4 alkynyl group, or (3) (a) -OR ³⁰ group, which is substituted by one group selected from (b) -NR ³¹ R ³² group and (c) Cyc3 C1~4 An alkyl group (wherein, R ^{30 to} R ³² each independently represent (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) Cyc3 or (4) a C1-4 alkyl substituted by Cyc3; Cyc3 represents (1) a C5-6 monocyclic carbocycle or (2) a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom. (However, the carbocycle or heterocycle may be substituted with a C1-4 alkoxy group.).
R ³ and R ⁴ are each independently:
(1) a hydrogen atom,
(2) a C1-4 alkyl group, or (3) a C1-4 alkyl group substituted by one or two groups arbitrarily selected from (a) Cyc2 and (b) a hydroxyl group (wherein Cyc2 is (1) a C5-6 monocyclic carbocycle or (2) a 5- to 6-membered monocyclic heterocycle containing 1-2 nitrogen atoms and / or one oxygen atom.)
R ³ and R ⁴ together

(Wherein, R ²⁶ represents a C1-4 alkyl group or Cyc2),
R ⁵ represents a hydrogen atom or a C1~4 alkyl group. ]
, A quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof (provided that (3R) -1-butyl-2,5-dioxo-3) Represents-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane hydrochloride. Make it not exist.). The compound according to claim 1, wherein R ³ and R ⁴ are hydrogen atoms, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof. R ³ is a hydrogen atom, substituted by one or two groups selected R ⁴ is (1) C1 -4 alkyl or (2) from (a) Cyc2 and (b) a hydroxyl group, optionally C1 The compound according to claim 1, which is an alkyl group, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof. R ³ and R ⁴ are each independently:
The (1) C1-4 alkyl group or (2) a C1-4 alkyl group substituted by one or two groups arbitrarily selected from (a) Cyc2 and (b) a hydroxyl group. The compound, its quaternary ammonium salt, its N-oxide, or its non-toxic salt. R ³ and R ⁴ together

(Wherein R ²⁶ has the same meaning as described in claim 1), a compound thereof, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof. Compound
(1) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9-benzyl-1,4,9-triazaspiro [5.5] Undecane,
(2) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(3) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(4) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(5) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-fluorophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(6) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(7) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylcarbonyl) phenylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane,
(8) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(9) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(10) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridin-3-yloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(11) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(12) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxypiperidin-1-ylmethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(13) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(14) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(15) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(16) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylthiophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(17) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(18) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-cyanophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(19) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (phenylthio) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane,
(20) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(21) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylsulfonyl) Aminophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(22) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(23) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(24) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (6-methylpyridine-1-oxide-3 -Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(25) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(26) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (6- (4-methoxyphenyloxy) pyridine-3- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(27) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (methyl Aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(28) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N -Methyl-N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(29) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(30) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(31) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -(Morpholin-4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(32) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(33) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(34) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(35) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(36) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(37) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(38) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(39) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N , N-diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(40) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4 -Methylpiperazin-1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(41) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (5-chloro-3-methyl-1-phenylpyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(42) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(43) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(44) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2- (N, N- Dimethylamino) ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(45) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (pyridin-3-yloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(46) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(47) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(48) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (2,4- Difluorophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(49) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (pyridine-2- Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(50) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylamino Carbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(51) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4-cyclohexyloxyphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(52) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (3,4,5,6-tetrahydropyran -4-yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(53) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(54) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(55) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(56) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(57) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2 -Phenylethyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(58) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxy Carbonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(59) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(60) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonyl) Piperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(61) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(62) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-2-methylpropyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(63) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(64) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(65) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(66) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(67) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(68) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) Ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(69) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(70) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(71) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyridin-1-oxide-3-yloxy) phenylmethyl) -1,4, 9-triazaspiro [5.5] undecane,
(72) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(73) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(74) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N, N-diethylaminosulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(75) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(76) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(77) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(78) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(79) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(80) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(81) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(82) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(83) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(84) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(85) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4 9-triazaspiro [5.5] undecane,
(86) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(87) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(88) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(89) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) Propylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(90) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(91) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(92) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(93) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) Aminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(94) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(95) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(96) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(97) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(98) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(99) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) )) Propylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(100) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(101) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′, N′-dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(102) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(103) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane,
(104) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(105) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(106) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) -2E- Propenyl) -1,4,9-triazaspiro [5.5] undecane;
(107) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(108) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (3- (3,5-dimethyl-1-phenylpyrazol-4-yl) propyl)- 1,4,9-triazaspiro [5.5] undecane,
(109) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenyl) pyrazole-4 -Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(110) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (pyrrolidin-1-ylcarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(111) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (morpholin-4-ylcarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(112) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) ethylaminocarbonyl )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(113) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (morpholin-4-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(114) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfonylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(115) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(116) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2- (morpholin-4-yl) ethylaminosulfonyl) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(117) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (4-methylpiperazin-1-ylsulfonyl) phenyl) pyrazole -4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(118) (3S) -1-Butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfinylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(119) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (2-hydroxyethylaminocarbonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(120) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (2-hydroxyethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(121) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (pyrrolidin-1-ylcarbonyl) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(122) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (cyclohexylaminosulfonyl) phenyl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(123) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3-methoxypropylaminosulfonyl) phenyl) pyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(124) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-methylsulfinylphenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(125) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-propylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(126) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-ethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(127) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclopentylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(128) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (morpholin-4-yl) propylaminosulfonyl) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(129) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N, N-dimethylaminosulfonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(130) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (pyrrolidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(131) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4- (N, N-dimethylamino) phenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(132) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(133) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxycarbonylphenyl) pyrazol-4-ylmethyl) -1,4 , 9-Triazaspiro [5.5] undecane,
(134) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(135) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (N-methyl-N- (2- (pyridin-2-yl) ethyl) aminocarbonyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(136) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((4-methoxyphenyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [ 5.5] Undecane,
(137) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(138) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methoxyphenyl) pyrazol-4-ylmethyl) -1,4, 9-triazaspiro [5.5] undecane,
(139) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylpiperidin-4-yl) pyrazol-4-ylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(140) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-methylsulfonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(141) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (3- (N, N-dimethylamino) propylaminosulfonyl) )) Phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(142) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4- (N-methyl-N- (2- (N ′, N′-dimethylamino) ethyl) aminosulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(143) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (piperidin-1-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(144) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (morpholin-4-ylcarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(145) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-((N, N-dimethylamino) methyl) phenyloxy) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(146) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (4-methylaminocarbonylphenyl) pyrazol-4-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(147) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1,1-dimethylethyl) pyrazol-4-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(148) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1- (1-benzyloxycarbonylpiperidin-4-yl) pyrazol-4-ylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(149) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5 ] Undecane,
(150) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-((methoxycarbonyl) methylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(151) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (carboxymethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(152) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenyloxyphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(153) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6-phenyloxypyridin-3-ylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(154) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-fluorophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(155) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-chlorophenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(156) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-cyanophenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(157) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(158) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridin-3-yloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(159) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-methylethyl) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(160) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(161) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3,4,5,6-tetrahydropyran -4-yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(162) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-phenylcarbonylphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(163) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (1-phenyl-1-hydroxymethyl) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(164) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(165) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylamino) Sulfonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(166) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N -Methyl-N- (2-hydroxyethyl) aminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(167) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (pyridine-2- Yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(168) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(169) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,3,5-trimethylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(170) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(171) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-bismethylsulfonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(172) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylsulfonyl) Aminophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(173) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(174) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(175) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (morpholine -4-ylcarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(176) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-aminocarbonylphenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(177) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(178) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-aminosulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(179) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (6-methylpyridine-1-oxide-3) -Yloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(180) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(181) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-hydroxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(182) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(183) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (pyrrolidine) -1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(184) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (5-chloro-3-methyl-1-phenylpyrazole- 4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(185) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(186) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(187) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N, N-dimethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(188) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(189) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(190) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-fluorophenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(191) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (6- (4-methoxyphenyloxy) pyridine-3- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(192) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(193) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2- (N, N- Dimethylamino) ethylaminocarbonyl) phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(194) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -Hydroxyethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(195) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(196) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(Morpholin-4-yl) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(197) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (morpholin-4-ylcarbonyl)) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(198) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (1,4-benzodioxan-6-ylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(199) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-diethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(200) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (pyridine-1-oxide-3-yloxy) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(201) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (4 -Methylpiperazin-1-ylsulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(202) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(203) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2,4- Difluorophenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(204) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (2 -(N, N-dimethylamino) ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(205) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methylamino) Carbonylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(206) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(207) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4-((4-methoxyphenyl) methylaminocarbonyl) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(208) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (3-methoxypropylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(209) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (N-methyl-N- (2- ( Pyridin-2-yl) ethyl) aminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(210) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (pyrrolidin-1-ylcarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(211) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-chlorophenyl) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(212) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-trifluoro Methylphenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(213) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4-methoxyphenyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(214) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-ethylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(215) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-propylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(216) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1,1- Dimethylethyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(217) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclopentylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(218) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (2-phenylethyl) ) Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(219) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-benzyloxy Carbonylpiperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(220) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (cyclohexylaminocarbonyl) phenylmethyl) -1, 4,9-triazaspiro [5.5] undecane,
(221) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (1-methylsulfonyl) Piperidin-4-yl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(222) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (2-hydroxyethylaminocarbonyl) Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(223) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-hydroxymethylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(224) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(225) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(226) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(227) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(228) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(3,5-dimethyl-1- (4- (N, N-dimethylaminocarbonyl) phenylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(229) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(230) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1- (3,4,5,6-tetrahydropyran-4-yl) methyl) -9 -(4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(231) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (3,5-dimethyl-1-phenylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(232) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4- (4-methoxyphenylmethylaminocarbonyl) ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(233) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(234) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclopentylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(235) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(236) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(237) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-2-methylpropyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(238) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(239) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-cyclohexylpyrazole-4- Ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(240) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(241) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1- (4- (N , N-dimethylaminocarbonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(242) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(243) (3R) -1-propyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(244) (3R) -1-propyl-2,5-dioxo-3- (1-cyclohexylmethylidene) -9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(245) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(246) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9- Triazaspiro [5.5] undecane,
(247) (3S) -1-propyl-2,5-dioxo-3- (2-methylpropyl) -9- (3,5-dimethyl-1- (4- (2- (N, N-dimethylamino) )) Ethylaminosulfonyl) phenyl) pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(248) (3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5 .5] undecane,
(249) (3S) -1-propyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(250) 1-butyl-2,5-dioxo-9- (4- (4-methylsulfonylaminophenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(251) 1-butyl-2,5-dioxo-9- (3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(252) (3R) -1- (2-butynyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenyl Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(253) (3S) -1- (2-butynyl) -2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (3,5-dimethyl-1-phenyl Pyrazol-4-ylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(254) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5.5] undecane ,
(255) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-phenyloxyphenyl) ethyl) -1,4,9-triazaspiro [5 .5] undecane,
(256) (3S) -1-butyl-2,5-dioxo-3- (2-methylpropyl) -9- (2- (4-methoxyphenyl) ethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(257) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4-ethoxycarbonylphenyl) -1,4,9-triazaspiro [5.5] undecane,
(258) (3S) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-4-methyl-9- (4-phenyloxyphenylmethyl) -1,4,9-triazaspiro [5.5] undecane ,
(259) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methylpropanoylamino) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(260) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-methoxyacetylamino) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(261) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2-phenylacetylamino) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(262) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (2- (4-fluorophenyl) acetylamino ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(263) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxycarbonylphenylaminocarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(264) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methoxyphenylmethyloxycarbonyl) phenylmethyl ) -1,4,9-Triazaspiro [5.5] undecane;
(265) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (2- (4-methylaminocarbonylphenyloxy) pyridine- 5-ylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(266) (3S) -1-butyl-2,5-dioxo-3-((1S) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-carboxyphenyloxy) phenylmethyl)- 1,4,9-triazaspiro [5.5] undecane,
(267) (3S) -1-butyl-2,5-dioxo-3- (pyridin-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(268) (3S) -1-butyl-2,5-dioxo-3-phenylmethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(269) (3S) -1-butyl-2,5-dioxo-3- (pyridin-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9 -Triazaspiro [5.5] undecane,
(270) (3S) -1-butyl-2,5-dioxo-3-hydroxymethyl-9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(271) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(272) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-3-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane,
(273) (3R) -1- (4-methoxyphenylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(274) (3R) -1-phenylmethyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenyl Methyl) -1,4,9-triazaspiro [5.5] undecane,
(275) (3R) -1- (2-methoxyethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonyl Phenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane,
(276) (3R) -1- (pyridin-2-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(277) (3R) -1- (pyridin-3-ylmethyl) -2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylamino Carbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(278) (3R) -1-butyl-2,5-dioxo-3-cyclohexylmethyl-9- (4- (4-carboxyphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5.5] Undecane,
(279) (3S) -1-butyl-2,5-dioxo-3- (pyridin-1-oxide-2-ylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1 , 4,9-Triazaspiro [5.5] undecane-9-oxide,
(280) 1-butyl-2,5-dioxo-3- (morpholin-4-ylmethyl) 9- (4- (4-methylaminocarbonylphenyloxy) phenylmethyl) -1,4,9-triazaspiro [5. 5] Undecane,
(281) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4- (N-hydroxycarbamoyl) phenyloxy ) Phenylmethyl) -1,4,9-triazaspiro [5.5] undecane;
(282) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenylcarbonyl ) -1,4,9-Triazaspiro [5.5] undecane;
(283) (3R) -1-butyl-2,5-dioxo-3-((1R) -1-hydroxy-1-cyclohexylmethyl) -9- (4- (4-methylaminocarbonylphenyloxy) phenyl) -1,4,9-triazaspiro [5.5] undecane,
The compound according to claim 1, which is a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof.   A drug containing the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) according to claim 1, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof as an active ingredient. Composition.   A chemokine containing the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) according to claim 1, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof as an active ingredient. / Control agents for the action of chemokine receptors. An asthma containing the triazaspiro [5.5] undecane derivative compound represented by the general formula (I) according to claim 1, a quaternary ammonium salt thereof, an N-oxide thereof, or a non-toxic salt thereof as an active ingredient. , Atopic dermatitis, hives, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteropathy, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, ischemia reperfusion injury Suppression, multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome, shock due to bacterial infection, diabetes, treatment of autoimmune diseases, transplant rejection, immunosuppression, prevention of cancer metastasis, prevention of acquired immunodeficiency syndrome And / or therapeutic agents.