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WO2013157622A1 - Inhibiteur de la réplication du vih - Google Patents

Inhibiteur de la réplication du vih Download PDF

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Publication number
WO2013157622A1
WO2013157622A1 PCT/JP2013/061575 JP2013061575W WO2013157622A1 WO 2013157622 A1 WO2013157622 A1 WO 2013157622A1 JP 2013061575 W JP2013061575 W JP 2013061575W WO 2013157622 A1 WO2013157622 A1 WO 2013157622A1
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Prior art keywords
substituted
unsubstituted
group
aromatic heterocyclic
compound
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PCT/JP2013/061575
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English (en)
Japanese (ja)
Inventor
杉山　修一
俊行 秋山
善之 垰田
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塩野義製薬株式会社
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Publication of WO2013157622A1 publication Critical patent/WO2013157622A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to a novel compound having an antiviral action, and more particularly to an anti-HIV drug.
  • HIV human immunodeficiency virus
  • AIDS acquired immunodeficiency syndrome
  • anti-HIV drugs reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors are clinically used, but drugs having the same mechanism of action often show cross-resistance or have additional effects. However, development of anti-HIV drugs having different mechanisms of action is desired.
  • Patent Document 1 reports a compound having a carboxymethylbenzene skeleton as an HIV reverse transcriptase inhibitor. Further, as an HIV replication inhibitor having a structure relatively similar to that of the present invention, carboxymethylpyridine derivatives (Patent Documents 2 to 8, 14, 19), carboxymethylpyrimidine derivatives (Patent Documents 8 to 11), phenylacetic acid derivatives (patents) Documents 12 to 13), tricyclic carboxymethylpyridine derivatives (Patent Document 15), carboxymethylpyridone derivatives (Patent Document 16), substituted five-membered ring compounds (Patent Document 17) and substituted six-membered ring compounds (Patent Document 18) has been reported. Patent Document 18 widely discloses six-membered ring compounds, and Patent Documents 2 to 8, 14, and 19 widely disclose pyridine derivatives, but any of the pyridine derivatives having a carboxymethyl structure at the 4-position. It is not described in the literature.
  • Patent Document 20 describes a compound having a structure relatively similar to that of the present invention, but is a document relating to an anticancer drug.
  • Non-Patent Documents 1 and 2 describe compounds that are relatively similar in structure to the present invention, but are related to synthesis techniques.
  • Patent Document 21 International Application PCT / JP2012 / 0775544, Japanese Patent Application No. 2013-016433, Japanese Patent Application No. 2013-071415.
  • An object of the present invention is to provide a novel compound having antiviral activity.
  • the present invention more preferably provides an anti-HIV drug having an HIV replication inhibitory action.
  • the compounds of the present invention and medicaments containing them are antiviral drugs (eg, antiretroviral drugs, anti-HIV drugs, anti-HTLV-1 (Human T cell leukemia virus type 1: human T cell leukemia virus type 1) , Anti-FIV (Feline immunodefectivity virus: feline AIDS virus) drug, anti-SIV (Simian immunodefectivity virus: salid AIDS virus) drug, particularly anti-HIV drug, anti-AIDS drug, or related diseases
  • antiviral drugs eg, antiretroviral drugs, anti-HIV drugs, anti-HTLV-1 (Human T cell leukemia virus type 1: human T cell leukemia virus type 1) , Anti-FIV (Feline immunodefectivity virus: feline AIDS virus) drug, anti-SIV (Simian immunodefectivity virus: salid AIDS virus) drug, particularly anti-HIV drug, anti-AIDS drug, or related diseases
  • antiviral drugs eg, antiretroviral drugs, anti-HIV
  • R 1 is a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group,
  • Each R 2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted or
  • R 4 represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle
  • a formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R 5 is absent, hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted unsubstituted An aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-ar
  • R 61 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R 62 —CO—, —CO—NR 62 —, —CH 2 —CO—NR 62 —, —NR 63 —CO—NR 62 —, —NR 62 —CS—, —CS—NR 62 —, —NR 63 — CS—NR 62 —, —NR 62 —SO 2 —, —SO 2 —NR 62 —, or —NR 63 —SO 2 —NR 62 —,
  • R 71 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle
  • R 72 and R 73 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle
  • R 72 and R 73 are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted
  • NR 72 -, - NR 73 -CO -NR 72 -, - NR 72 -CS -, - CS-NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, - SO 2 - NR 72 -, or -NR 73 -SO 2 -NR 72 - is a compound or a pharmaceutically acceptable salt thereof according to any one of the above (1) to (8), (10) R 7 is —Z 7 —R 71 , Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, The compound according to the above (9), which is —NR 73 —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 —SO 2 —NR 72 — Its pharmaceutically acceptable
  • X is —C (R 10 ) 2 —, —NR 9 —, or —O—
  • Y is —C (R 10 ) 2 —, —CO—, or —SO 2 —
  • W is —C (R 10 ) 2 —, —NR 10 —, or —O—
  • R 9 is halogen, cyano, nitro, or —Z 9 —R 91 ,
  • Z 9 is a single bond, —O—, —S—, —NR 92 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR.
  • R 91 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R 92
  • R 8 Indicated by one of the R 8 is halogen, cyano, nitro, or —Z 8 —R 81 ;
  • Z 8 is a single bond, —O—, —S—, —NR 82 —, —CO—, —CS—, —SO 2 —, —O—CO—, —CO—O—, —NR.
  • R 81 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocycle A formula group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, R 82
  • R 1 and R 7 together with the adjacent carbon atom form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group, and R 2 is substituted Or unsubstituted alkyloxy, n is 1, and R 3 is substituted or unsubstituted phenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted chromanyl, or substituted or unsubstituted benzomorpholinyl
  • R 4 is a hydrogen atom
  • R 5 is absent
  • R 6 is a substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof Salt
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n 1, and R 3 is substituted or unsubstituted
  • the compound of the present invention has replication inhibitory activity against viruses, particularly HIV (eg, HIV-1) and its resistant viruses. Therefore, it is useful for prevention or treatment of viral infections (eg AIDS).
  • viruses particularly HIV (eg, HIV-1) and its resistant viruses. Therefore, it is useful for prevention or treatment of viral infections (eg AIDS).
  • Halogen includes fluorine atom, chlorine atom, bromine atom, and iodine atom. In particular, a fluorine atom and a chlorine atom are preferable.
  • Alkyl includes straight or branched hydrocarbon groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and still more preferably 1 to 4 carbon atoms. To do. For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl , Isooctyl, n-nonyl, n-decyl and the like.
  • alkyl examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and n-pentyl. Further preferred examples include methyl, ethyl, n-propyl, isopropyl and tert-butyl.
  • Alkenyl has 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and further preferably 2 to 4 carbon atoms, having one or more double bonds at any position. These linear or branched hydrocarbon groups are included.
  • alkenyl include vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, decenyl, tridecenyl, decenyl Etc.
  • alkenyl include vinyl, allyl, propenyl, isopropenyl and butenyl.
  • Alkynyl has 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and more preferably 2 to 4 carbon atoms, having one or more triple bonds at any position. Includes straight chain or branched hydrocarbon groups. Examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl and the like. These may further have a double bond at an arbitrary position. Preferred embodiments of “alkynyl” include ethynyl, propynyl, butynyl and pentynyl.
  • Alkylene is a straight or branched divalent hydrocarbon having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and still more preferably 1 to 4 carbon atoms. Includes groups. Examples include methylene, ethylene, trimethylene, propylene, tetramethylene, pentamethylene, hexamethylene and the like.
  • alkenylene refers to a carbon number of 2 to 15, preferably 2 to 10, more preferably 2 to 6 and even more preferably 2 to 4 having one or more double bonds at an arbitrary position. And a linear or branched divalent hydrocarbon group.
  • vinylene, propenylene, butenylene, pentenylene and the like can be mentioned.
  • Alkynylene refers to carbon atoms of 2 to 15, preferably 2 to 10, more preferably 2 to 6, more preferably 2 to 4 carbon atoms having one or more triple bonds at any position.
  • a linear or branched divalent hydrocarbon group is included. These may further have a double bond at an arbitrary position. For example, ethynylene, propynylene, butynylene, pentynylene, hexynylene and the like can be mentioned.
  • Aromatic carbocyclic group means a monocyclic or bicyclic or more aromatic hydrocarbon group. For example, phenyl, naphthyl, anthryl, phenanthryl and the like can be mentioned. A preferred embodiment of the “aromatic carbocyclic group” includes phenyl.
  • non-aromatic carbocyclic group means a non-aromatic saturated hydrocarbon group or non-aromatic unsaturated hydrocarbon group having one or more rings.
  • the non-aromatic carbocyclic group having 2 or more rings also includes those in which the ring in the above “aromatic carbocyclic group” is condensed with a monocyclic or 2 or more non-aromatic carbocyclic groups.
  • the “non-aromatic carbocyclic group” includes a group that forms a bridge or a spiro ring as described below.
  • the monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and still more preferably 4 to 8 carbon atoms.
  • cycloalkyl, cycloalkenyl and the like can be mentioned.
  • Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like.
  • “Cycloalkenyl” includes cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like.
  • Examples of the two or more non-aromatic carbocyclic groups include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl, dihydroindenyl and the like.
  • “Aromatic heterocyclic group” means a monocyclic or bicyclic or more aromatic cyclic group having one or more heteroatoms arbitrarily selected from O, S and N in the ring To do.
  • the aromatic heterocyclic group having two or more rings includes those obtained by condensing a ring in the above “aromatic carbocyclic group” to a monocyclic or two or more aromatic heterocyclic group.
  • the monocyclic aromatic heterocyclic group is preferably 5 to 8 members, more preferably 5 or 6 members.
  • Examples include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, and the like.
  • bicyclic aromatic heterocyclic group examples include indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzisoxazolyl, Oxazolyl, benzoxiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyr Dazinyl, oxazolopyridyl, thiazolopyridyl and the like can be mentioned.
  • aromatic heterocyclic group having 3 or more rings examples include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, dibenzofuryl and the like.
  • Non-aromatic heterocyclic group means a monocyclic or bicyclic or more non-aromatic cyclic group having one or more of the same or different heteroatoms arbitrarily selected from O, S and N in the ring Means.
  • the non-aromatic heterocyclic group having 2 or more rings is a monocyclic or 2 or more non-aromatic heterocyclic group, the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group”, and Also included are those in which each ring in the “aromatic heterocyclic group” is condensed.
  • the “non-aromatic heterocyclic group” includes a group which forms a bridge or a spiro ring as described below.
  • the monocyclic non-aromatic heterocyclic group is preferably 3 to 8 members, more preferably 5 or 6 members.
  • non-aromatic heterocyclic group having two or more rings examples include indolinyl, isoindolinyl, chromanyl, isochromanyl, dihydrobenzofuryl, benzodioxolyl, benzodioxanyl, benzomorpholinyl and the like.
  • “Hydroxyalkyl” means a group in which one or more hydroxy groups are replaced with a hydrogen atom bonded to a carbon atom of the “alkyl”. Examples thereof include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 1,2-hydroxyethyl and the like. A preferred embodiment of “hydroxyalkyl” includes hydroxymethyl.
  • Alkyloxy means a group in which the above “alkyl” is bonded to an oxygen atom. Examples thereof include methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, tert-butyloxy, isobutyloxy, sec-butyloxy, pentyloxy, isopentyloxy, hexyloxy and the like. Preferable embodiments of “alkyloxy” include methoxy, ethoxy, n-propyloxy, isopropyloxy, tert-butyloxy.
  • Alkenyloxy means a group in which the above “alkenyl” is bonded to an oxygen atom.
  • vinyloxy, allyloxy, 1-propenyloxy, 2-butenyloxy, 2-pentenyloxy, 2-hexenyloxy, 2-heptenyloxy, 2-octenyloxy and the like can be mentioned.
  • Alkynyloxy means a group in which the above “alkynyl” is bonded to an oxygen atom. Examples include ethynyloxy, 1-propynyloxy, 2-propynyloxy, 2-butynyloxy, 2-pentynyloxy, 2-hexynyloxy, 2-heptynyloxy, 2-octynyloxy and the like.
  • Haloalkyl means a group in which one or more of the above “halogens” are bonded to the above “alkyl”. For example, monofluoromethyl, monofluoroethyl, monofluoropropyl, 2,2,3,3,3-pentafluoropropyl, monochloromethyl, trifluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2, Examples include 2,2-trichloroethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropan-2-yl and the like. Preferable embodiments of “haloalkyl” include trifluoromethyl and trichloromethyl.
  • Haloalkyloxy means a group in which the above “haloalkyl” is bonded to an oxygen atom. Examples thereof include monofluoromethoxy, monofluoroethoxy, trifluoromethoxy, trichloromethoxy, trifluoroethoxy, trichloroethoxy and the like. Preferable embodiments of “haloalkyloxy” include trifluoromethoxy and trichloromethoxy.
  • Alkyloxyalkyl means a group in which the above “alkyloxy” is bonded to the above “alkyl”. For example, methoxymethyl, methoxyethyl, ethoxymethyl and the like can be mentioned.
  • Alkyloxyalkyloxy means a group in which the “alkyloxy” is bonded to the “alkyloxy”. Examples thereof include methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy and the like.
  • Alkylcarbonyl means a group in which the above “alkyl” is bonded to a carbonyl group. Examples thereof include methylcarbonyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, tert-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, pentylcarbonyl, isopentylcarbonyl, hexylcarbonyl and the like. Preferable embodiments of “alkylcarbonyl” include methylcarbonyl, ethylcarbonyl, and n-propylcarbonyl.
  • Alkenylcarbonyl means a group in which the above “alkenyl” is bonded to a carbonyl group.
  • alkenyl ethylenylcarbonyl, propenylcarbonyl and the like can be mentioned.
  • Alkynylcarbonyl means a group in which the above “alkynyl” is bonded to a carbonyl group. For example, ethynylcarbonyl, propynylcarbonyl and the like can be mentioned.
  • “Monoalkylamino” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. For example, methylamino, ethylamino, isopropylamino and the like can be mentioned. Preferable embodiments of “monoalkylamino” include methylamino and ethylamino.
  • Dialkylamino means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkyl groups may be the same or different. Examples include dimethylamino, diethylamino, N, N-diisopropylamino, N-methyl-N-ethylamino, N-isopropyl-N-ethylamino and the like. Preferred embodiments of “dialkylamino” include dimethylamino and diethylamino.
  • Alkylsulfonyl means a group in which the above “alkyl” is bonded to a sulfonyl group.
  • methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, tert-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl and the like can be mentioned.
  • Preferable embodiments of “alkylsulfonyl” include methylsulfonyl and ethylsulfonyl.
  • Alkenylsulfonyl means a group in which the above “alkenyl” is bonded to a sulfonyl group.
  • alkenyl ethylenylsulfonyl, propenylsulfonyl and the like can be mentioned.
  • Alkynylsulfonyl means a group in which the above “alkynyl” is bonded to a sulfonyl group. For example, ethynylsulfonyl, propynylsulfonyl and the like can be mentioned.
  • “Monoalkylcarbonylamino” means a group in which the above “alkylcarbonyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group.
  • methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, tert-butylcarbonylamino, isobutylcarbonylamino, sec-butylcarbonylamino and the like can be mentioned.
  • Preferable embodiments of “monoalkylcarbonylamino” include methylcarbonylamino and ethylcarbonylamino.
  • Dialkylcarbonylamino means a group in which the above “alkylcarbonyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkylcarbonyl groups may be the same or different. For example, dimethylcarbonylamino, diethylcarbonylamino, N, N-diisopropylcarbonylamino and the like can be mentioned. Preferred embodiments of “dialkylcarbonylamino” include dimethylcarbonylamino and diethylcarbonylamino.
  • “Monoalkylsulfonylamino” means a group in which the above “alkylsulfonyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group. Examples include methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, tert-butylsulfonylamino, isobutylsulfonylamino, sec-butylsulfonylamino and the like. Preferable embodiments of “monoalkylsulfonylamino” include methylsulfonylamino and ethylsulfonylamino.
  • Dialkylsulfonylamino means a group in which the above “alkylsulfonyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the amino group. Two alkylsulfonyl groups may be the same or different. For example, dimethylsulfonylamino, diethylsulfonylamino, N, N-diisopropylsulfonylamino and the like can be mentioned. Preferred embodiments of “dialkylcarbonylamino” include dimethylsulfonylamino and diethylsulfonylamino.
  • Alkylimino means a group in which the above “alkyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • methylimino, ethylimino, n-propylimino, isopropylimino and the like can be mentioned.
  • Alkenylimino means a group in which the above “alkenyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. Examples thereof include ethylenylimino and propenylimino.
  • Alkynylimino means a group in which the above “alkynyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • alkynylimino ethynylimino, propynylimino and the like can be mentioned.
  • Alkylcarbonylimino means a group in which the above “alkylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • methylcarbonylimino, ethylcarbonylimino, n-propylcarbonylimino, isopropylcarbonylimino and the like can be mentioned.
  • Alkenylcarbonylimino means a group in which the above “alkenylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • alkenylcarbonylimino ethylenylcarbonylimino, propenylcarbonylimino and the like can be mentioned.
  • Alkynylcarbonylimino means a group in which the above “alkynylcarbonyl” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • alkynylcarbonylimino ethynylcarbonylimino, propynylcarbonylimino and the like can be mentioned.
  • Alkyloxyimino means a group in which the above “alkyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group. Examples thereof include methyloxyimino, ethyloxyimino, n-propyloxyimino, isopropyloxyimino and the like.
  • Alkenyloxyimino means a group in which the above “alkenyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • alkenyloxyimino ethylenyloxyimino, propenyloxyimino and the like can be mentioned.
  • Alkynyloxyimino means a group in which the above “alkynyloxy” is replaced with a hydrogen atom bonded to the nitrogen atom of the imino group.
  • alkynyloxyimino ethynyloxyimino, propynyloxyimino and the like can be mentioned.
  • Alkylcarbonyloxy means a group in which the above “alkylcarbonyl” is bonded to an oxygen atom.
  • methylcarbonyloxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, tert-butylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyloxy and the like can be mentioned.
  • Preferable embodiments of “alkylcarbonyloxy” include methylcarbonyloxy and ethylcarbonyloxy.
  • Alkenylcarbonyloxy means a group in which the above “alkenylcarbonyl” is bonded to an oxygen atom.
  • alkenylcarbonyl ethylenylcarbonyloxy, propenylcarbonyloxy and the like can be mentioned.
  • Alkynylcarbonyloxy means a group in which the above “alkynylcarbonyl” is bonded to an oxygen atom.
  • alkynylcarbonyloxy ethynylcarbonyloxy, propynylcarbonyloxy and the like can be mentioned.
  • Alkyloxycarbonyl means a group in which the above “alkyloxy” is bonded to a carbonyl group. For example, methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, tert-butyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, hexyloxycarbonyl, etc. It is done.
  • Preferable embodiments of “alkyloxycarbonyl” include methyloxycarbonyl, ethyloxycarbonyl, and propyloxycarbonyl.
  • Alkenyloxycarbonyl means a group in which the above “alkenyloxy” is bonded to a carbonyl group. For example, ethylenyloxycarbonyl, propenyloxycarbonyl and the like can be mentioned.
  • Alkynyloxycarbonyl means a group in which the above “alkynyloxy” is bonded to a carbonyl group. For example, ethynyloxycarbonyl, propynyloxycarbonyl and the like can be mentioned.
  • Alkylsulfanyl means a group in which the above “alkyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl and the like can be mentioned.
  • Alkenylsulfanyl means a group in which the above “alkenyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • alkenyl ethylenylsulfanyl, propenylsulfanyl and the like can be mentioned.
  • Alkynylsulfanyl means a group in which the above “alkynyl” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • alkynylsulfanyl ethynylsulfanyl, propynylsulfanyl and the like can be mentioned.
  • Alkylsulfinyl means a group in which the above “alkyl” is bonded to a sulfinyl group. Examples thereof include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl and the like.
  • Alkenylsulfinyl means a group in which the above “alkenyl” is bonded to a sulfinyl group.
  • alkenyl ethylenylsulfinyl, propenylsulfinyl and the like can be mentioned.
  • Alkynylsulfinyl means a group in which the above “alkynyl” is bonded to a sulfinyl group. For example, ethynylsulfinyl, propynylsulfinyl and the like can be mentioned.
  • “Monoalkylcarbamoyl” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the carbamoyl group. Examples thereof include methylcarbamoyl and ethylcarbamoyl.
  • Dialkylcarbamoyl means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the carbamoyl group.
  • Two alkyl groups may be the same or different. Examples thereof include dimethylcarbamoyl, diethylcarbamoyl and the like.
  • “Monoalkylsulfamoyl” means a group in which the above “alkyl” is replaced with one hydrogen atom bonded to the nitrogen atom of the sulfamoyl group. For example, methylsulfamoyl, dimethylsulfamoylmoyl, etc. are mentioned.
  • Dialkylsulfamoyl means a group in which the above “alkyl” is replaced with two hydrogen atoms bonded to the nitrogen atom of the sulfamoyl group.
  • Two alkyl groups may be the same or different. Examples thereof include dimethylcarbamoyl, diethylcarbamoyl and the like.
  • Trialkylsilyl means a group in which three of the above “alkyl” are bonded to a silicon atom.
  • the three alkyls may be the same or different.
  • trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl and the like can be mentioned.
  • Aromatic carbocyclic alkyl “non-aromatic carbocyclic alkyl”, “aromatic heterocyclic alkyl”, and “non-aromatic heterocyclic alkyl”, “Aromatic carbocyclic alkyloxy”, “non-aromatic carbocyclic alkyloxy”, “aromatic heterocyclic alkyloxy”, and “non-aromatic heterocyclic alkyloxy”, “Aromatic carbocyclic alkylsulfanyl”, “non-aromatic carbocyclic alkylsulfanyl”, “aromatic heterocyclic alkylsulfanyl”, and “non-aromatic heterocyclic alkylsulfanyl”, “Aromatic carbocyclic alkyloxycarbonyl”, “non-aromatic carbocyclic alkyloxycarbonyl”, “aromatic heterocyclic alkyloxycarbonyl”, and “non-aromatic heterocyclic alkyloxycarbonyl”, “Aromatic
  • “Aromatic carbocyclic alkyl” means an alkyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyl, phenethyl, phenylpropynyl, benzhydryl, trityl, naphthylmethyl, groups shown below
  • aromatic carbocyclic alkyl examples include benzyl, phenethyl and benzhydryl.
  • Non-aromatic carbocyclic alkyl means alkyl substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • the “non-aromatic carbocyclic alkyl” also includes “non-aromatic carbocyclic alkyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, groups shown below
  • “Aromatic heterocyclic alkyl” means alkyl substituted with one or more of the above “aromatic heterocyclic groups”. “Aromatic heterocyclic alkyl” also includes “aromatic heterocyclic alkyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. .
  • pyridylmethyl furanylmethyl, imidazolylmethyl, indolylmethyl, benzothiophenylmethyl, oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, isothiazolylmethyl, pyrazolylmethyl, isopyrazolylmethyl, pyrrolidinylmethyl, benz Oxazolylmethyl, group shown below
  • Non-aromatic heterocyclic alkyl means alkyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl portion is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • non-aromatic heterocyclic alkyl For example, tetrahydropyranylmethyl, morpholinylethyl, piperidinylmethyl, piperazinylmethyl, groups shown below
  • “Aromatic carbocyclic alkyloxy” means alkyloxy substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxy, phenethyloxy, phenylpropynyloxy, benzhydryloxy, trityloxy, naphthylmethyloxy, groups shown below
  • Non-aromatic carbocyclic alkyloxy means alkyloxy substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • the “non-aromatic carbocyclic alkyloxy” also includes “non-aromatic carbocyclic alkyloxy” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyloxy, cyclobutylmethyloxy, cyclopentylmethyloxy, cyclohexylmethyloxy, groups shown below
  • “Aromatic heterocyclic alkyloxy” means alkyloxy substituted with one or more of the above “aromatic heterocyclic groups”. “Aromatic heterocyclic alkyloxy” also includes “aromatic heterocyclic alkyloxy” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Include.
  • Non-aromatic heterocyclic alkyloxy means alkyloxy substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”. It also includes “non-aromatic heterocyclic alkyloxy”. For example, tetrahydropyranylmethyloxy, morpholinylethyloxy, piperidinylmethyloxy, piperazinylmethyloxy, groups shown below
  • “Aromatic carbocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “aromatic carbocyclic groups”. Examples include benzylsulfanyl, phenethylsulfanyl, phenylpropynylsulfanyl, benzhydrylsulfanyl, tritylsulfanyl, naphthylmethylsulfanyl and the like.
  • Non-aromatic carbocyclic alkylsulfanyl means alkylsulfanyl substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • the “non-aromatic carbocyclic alkylsulfanyl” also includes “non-aromatic carbocyclic alkylsulfanyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. Examples thereof include cyclopropylmethylsulfanyl, cyclobutylmethylsulfanyl, cyclopentylmethylsulfanyl, cyclohexylmethylsulfanyl and the like.
  • “Aromatic heterocyclic alkylsulfanyl” means alkylsulfanyl substituted with one or more of the above “aromatic heterocyclic groups”.
  • “aromatic heterocyclic alkylsulfanyl” includes “aromatic heterocyclic alkylsulfanyl” in which an alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Include.
  • pyridylmethylsulfanyl furanylmethylsulfanyl, imidazolylmethylsulfanyl, indolylmethylsulfanyl, benzothiophenylmethylsulfanyl, oxazolylmethylsulfanyl, isoxazolylmethylsulfanyl, thiazolylmethylsulfanyl, isothiazolylmethylsulfanyl , Pyrazolylmethylsulfanyl, isopyrazolylmethylsulfanyl, pyrrolidinylmethylsulfanyl, benzoxazolylmethylsulfanyl and the like.
  • Non-aromatic heterocyclic alkylsulfanyl means alkylsulfanyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • non-aromatic heterocyclic alkylsulfanyl examples thereof include tetrahydropyranylmethylsulfanyl, morpholinylethylsulfanyl, piperidinylmethylsulfanyl, piperazinylmethylsulfanyl and the like.
  • “Aromatic carbocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxycarbonyl, phenethyloxycarbonyl, phenylpropynyloxycarbonyl, benzohydryloxycarbonyl, trityloxycarbonyl, naphthylmethyloxycarbonyl, groups shown below
  • Non-aromatic carbocyclic alkyloxycarbonyl means alkyloxycarbonyl substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • the “non-aromatic carbocyclic alkyloxycarbonyl” also includes “non-aromatic carbocyclic alkyloxycarbonyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group”. For example, cyclopropylmethyloxycarbonyl, cyclobutylmethyloxycarbonyl, cyclopentylmethyloxycarbonyl, cyclohexylmethyloxycarbonyl, groups shown below
  • “Aromatic heterocyclic alkyloxycarbonyl” means alkyloxycarbonyl substituted with one or more of the above “aromatic heterocyclic groups”.
  • the “aromatic heterocyclic alkyloxycarbonyl” is an “aromatic heterocyclic alkyloxycarbonyl” in which the alkyl moiety is substituted with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Is also included.
  • pyridylmethyloxycarbonyl furanylmethyloxycarbonyl, imidazolylmethyloxycarbonyl, indolylmethyloxycarbonyl, benzothiophenylmethyloxycarbonyl, oxazolylmethyloxycarbonyl, isoxazolylmethyloxycarbonyl, thiazolylmethyl Oxycarbonyl, isothiazolylmethyloxycarbonyl, pyrazolylmethyloxycarbonyl, isopyrazolylmethyloxycarbonyl, pyrrolidinylmethyloxycarbonyl, benzoxazolylmethyloxycarbonyl, groups shown below
  • Non-aromatic heterocyclic alkyloxycarbonyl means alkyloxycarbonyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • the alkyl moiety is substituted with the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic heterocyclic group”.
  • non-aromatic heterocyclic alkyloxycarbonyl For example, tetrahydropyranylmethyloxy, morpholinylethyloxy, piperidinylmethyloxy, piperazinylmethyloxy, groups shown below
  • “Aromatic carbocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “aromatic carbocyclic groups”. For example, benzyloxymethyl, phenethyloxymethyl, phenylpropynyloxymethyl, benzohydryloxymethyl, trityloxymethyl, naphthylmethyloxymethyl, groups shown below
  • Non-aromatic carbocyclic alkyloxyalkyl means alkyloxyalkyl substituted with one or more of the above “non-aromatic carbocyclic groups”.
  • non-aromatic carbocyclic alkyloxyalkyl means “non-aromatic carbocyclic alkyloxyalkyl” in which the alkyl moiety to which the non-aromatic carbocycle is bonded is substituted with the above “aromatic carbocyclic group”. Is also included. For example, cyclopropylmethyloxymethyl, cyclobutylmethyloxymethyl, cyclopentylmethyloxymethyl, cyclohexylmethyloxymethyl, groups shown below
  • “Aromatic heterocyclic alkyloxyalkyl” means alkyloxyalkyl substituted with one or more of the above “aromatic heterocyclic groups”.
  • the “aromatic heterocyclic alkyloxyalkyl” is obtained by replacing the alkyl moiety to which the aromatic heterocyclic ring is bonded with the above “aromatic carbocyclic group” and / or “non-aromatic carbocyclic group”. Also included are “aromatic heterocyclic alkyloxyalkyl”.
  • pyridylmethyloxymethyl furanylmethyloxymethyl, imidazolylmethyloxymethyl, indolylmethyloxymethyl, benzothiophenylmethyloxymethyl, oxazolylmethyloxymethyl, isoxazolylmethyloxymethyl, thiazolylmethyl Oxymethyl, isothiazolylmethyloxymethyl, pyrazolylmethyloxymethyl, isopyrazolylmethyloxymethyl, pyrrolidinylmethyloxymethyl, benzoxazolylmethyloxymethyl, groups shown below
  • Non-aromatic heterocyclic alkyloxyalkyl means alkyloxyalkyl substituted with one or more of the above “non-aromatic heterocyclic groups”.
  • “non-aromatic heterocyclic alkyloxy” means that the alkyl moiety to which the non-aromatic heterocyclic ring is bonded is the above “aromatic carbocyclic group”, “non-aromatic carbocyclic group” and / or “aromatic”.
  • non-aromatic heterocyclic alkyloxyalkyl substituted with “aromatic heterocyclic group”. For example, tetrahydropyranylmethyloxymethyl, morpholinylethyloxymethyl, piperidinylmethyloxymethyl, piperazinylmethyloxymethyl, groups shown below
  • “Aromatic carbocyclic alkylamino” means a group in which the above “aromatic carbocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. Examples include benzylamino, phenethylamino, phenylpropynylamino, benzohydrylamino, tritylamino, naphthylmethylamino, dibenzylamino and the like.
  • Non-aromatic carbocyclic alkylamino means a group in which the above “non-aromatic carbocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • cyclopropylmethylamino, cyclobutylmethylamino, cyclopentylmethylamino, cyclohexylmethylamino and the like can be mentioned.
  • “Aromatic heterocyclic alkylamino” means a group in which the above “aromatic heterocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • aromatic heterocyclic alkyl For example, pyridylmethylamino, furanylmethylamino, imidazolylmethylamino, indolylmethylamino, benzothiophenylmethylamino, oxazolylmethylamino, isoxazolylmethylamino, thiazolylmethylamino, isothiazolylmethylamino , Pyrazolylmethylamino, isopyrazolylmethylamino, pyrrolidinylmethylamino, benzoxazolylmethylamino and the like.
  • Non-aromatic heterocyclic alkylamino means a group in which the above “non-aromatic heterocyclic alkyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • tetrahydropyranylmethylamino, morpholinylethylamino, piperidinylmethylamino, piperazinylmethylamino and the like can be mentioned.
  • Aromatic carbocyclic oxy means a group in which an “aromatic carbocycle” is bonded to an oxygen atom. For example, phenyloxy, naphthyloxy and the like can be mentioned.
  • “Aromatic carbocyclic amino” means a group in which “aromatic carbocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. For example, phenylamino, naphthylamino and the like can be mentioned.
  • “Aromatic carbocyclic carbonyl” means a group in which an “aromatic carbocycle” is bonded to a carbonyl group. For example, phenylcarbonyl, naphthylcarbonyl and the like can be mentioned.
  • “Aromatic carbocyclic oxycarbonyl” means a group in which the above “aromatic carbocyclic oxy” is bonded to a carbonyl group.
  • Aromatic carbocyclic carbonylamino means a group in which the above “aromatic carbocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • phenylcarbonylamino, naphthylcarbonylamino and the like can be mentioned.
  • Aromatic carbocyclic sulfanyl means a group in which an “aromatic carbocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • phenylsulfanyl and naphthylsulfanyl examples thereof include phenylsulfanyl and naphthylsulfanyl.
  • “Aromatic carbocyclic sulfonyl” means a group in which “aromatic carbocycle” is bonded to a sulfonyl group.
  • aromatic carbocycle a group in which “aromatic carbocycle” is bonded to a sulfonyl group.
  • phenylsulfonyl, naphthylsulfonyl and the like can be mentioned.
  • Non-aromatic carbocyclic oxy means a group in which “non-aromatic carbocycle” is bonded to an oxygen atom.
  • Non-aromatic carbocyclic amino means a group in which “non-aromatic carbocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • Non-aromatic carbocycle carbonyl means a group in which “non-aromatic carbocycle” is bonded to a carbonyl group.
  • non-aromatic carbocyclic oxycarbonyl means a group in which the above “non-aromatic carbocyclic oxy” is bonded to a carbonyl group.
  • cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, cyclohexenyloxycarbonyl and the like can be mentioned.
  • non-aromatic carbocyclic carbonylamino means a group in which the above “non-aromatic carbocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group. Examples thereof include cyclopropylcarbonylamino, cyclohexylcarbonylamino, cyclohexenylcarbonylamino and the like.
  • Non-aromatic carbocyclic sulfanyl means a group in which a “non-aromatic carbocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • Non-aromatic carbocycle sulfonyl means a group in which “non-aromatic carbocycle” is bonded to a sulfonyl group. Examples include cyclopropylsulfonyl, cyclohexylsulfonyl, cyclohexenylsulfonyl and the like.
  • the “aromatic heterocycle” part of “aromatic heterocycle sulfonyl” is the same as the above “aromatic heterocycle”.
  • “Aromatic heterocycle oxy” means a group in which “aromatic heterocycle” is bonded to an oxygen atom. For example, pyridyloxy, oxazolyloxy and the like can be mentioned.
  • “Aromatic heterocycle amino” means a group in which “aromatic heterocycle” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • “Aromatic heterocycle carbonyl” means a group in which “aromatic heterocycle” is bonded to a carbonyl group.
  • “Aromatic heterocyclic oxycarbonyl” means a group in which the above “aromatic heterocyclic oxy” is bonded to a carbonyl group.
  • pyridyloxycarbonyl, oxazolyloxycarbonyl and the like can be mentioned.
  • “Aromatic heterocyclic carbonylamino” means a group in which the above “aromatic heterocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • pyridylcarbonylamino, oxazolylcarbonylamino and the like can be mentioned.
  • Aromatic heterocycle sulfanyl means a group in which an “aromatic heterocycle” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • pyridylsulfanyl, oxazolylsulfanyl and the like can be mentioned.
  • “Aromatic heterocycle sulfonyl” means a group in which “aromatic heterocycle” is bonded to a sulfonyl group.
  • pyridylsulfonyl, oxazolylsulfonyl and the like can be mentioned.
  • Non-aromatic heterocyclic oxy means a group in which “non-aromatic heterocyclic” is bonded to an oxygen atom.
  • Non-aromatic heterocyclic amino means a group in which “non-aromatic heterocyclic” is replaced with one hydrogen atom bonded to the nitrogen atom of the amino group.
  • Non-aromatic heterocyclic carbonyl means a group in which “non-aromatic heterocyclic” is bonded to a carbonyl group.
  • piperidinylcarbonyl, tetrahydrofurylcarbonyl and the like can be mentioned.
  • non-aromatic heterocyclic oxycarbonyl means a group in which the above “non-aromatic heterocyclic oxy” is bonded to a carbonyl group.
  • piperidinyloxycarbonyl, tetrahydrofuryloxycarbonyl and the like can be mentioned.
  • non-aromatic heterocyclic carbonylamino means a group in which the above “non-aromatic heterocyclic carbonyl” is replaced with one or two hydrogen atoms bonded to the nitrogen atom of the amino group.
  • piperidinylcarbonylamino, tetrahydrofurylcarbonylamino and the like can be mentioned.
  • Non-aromatic heterocyclic sulfanyl means a group in which a “non-aromatic heterocyclic ring” is replaced with a hydrogen atom bonded to a sulfur atom of a sulfanyl group.
  • piperidinylsulfanyl, tetrahydrofurylsulfanyl and the like can be mentioned.
  • Non-aromatic heterocyclic sulfonyl means a group in which “non-aromatic heterocyclic” is bonded to a sulfonyl group.
  • piperidinylsulfonyl, tetrahydrofurylsulfonyl and the like can be mentioned.
  • the carbon atom at any position may be bonded to one or more groups selected from the following substituents.
  • substituents halogen, hydroxy, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso , Azide, hydrazino, ureido, amidino, guanidino, trialkylsilyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, monoalkylamino, dialkylamino, alkylsulfonyl, alkeny
  • An atom at any position on the ring may be bonded to one or more groups selected from the following substituents.
  • substituents halogen, hydroxy, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso , Azide, hydrazino, ureido, amidino, guanidino, trialkylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy, alkyl
  • substituted or unsubstituted non-aromatic carbocyclic group and “substituted or unsubstituted non-aromatic heterocyclic group” may be substituted with “oxo”. In this case, it means a group in which two hydrogen atoms on a carbon atom are substituted as follows.
  • substituted or unsubstituted non-aromatic carbocyclic group and “substituted or unsubstituted non-aromatic heterocyclic group” are bridged by alkylene, alkenylene, or alkynylene, or other ring
  • a spiro ring may be formed together with cycloalkane, cycloalkene, cycloalkyne, oxirane, oxetane, thiirane and the like.
  • R 1 is preferably a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted Or an unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably a substituted or unsubstituted alkyl , Substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, more preferably substituted or unsubstituted alkyl, particularly preferably alkyl having 1 to 4 carbon atoms, most preferably methyl. It is.
  • R 2 is each independently preferably substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted Or an unsubstituted alkynyloxy, a substituted or unsubstituted alkylsulfanyl, a substituted or unsubstituted alkenylsulfanyl, or a substituted or unsubstituted alkynylsulfanyl, more preferably a substituted or unsubstituted alkyloxy, substituted or unsubstituted Alkenyloxy, or substituted or unsubstituted alkynyloxy, more preferably substituted or unsubstituted alkyloxy, particularly preferably alkyloxy having 1 to 4 carbon atoms, and most preferably tert- The Til
  • N is preferably 1 or 2, particularly preferably 1.
  • R 3 is preferably a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted A non-aromatic heterocyclic group, more preferably a substituted or unsubstituted phenyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted chromanyl, or a substituted or unsubstituted benzomorpholinyl; Preferred is substituted or unsubstituted phenyl or substituted or unsubstituted chromanyl.
  • substituents are halogen, hydroxy, amino, cyano, oxo, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkyloxy, alkenyloxy, alkynyloxy, alkyloxyalkyl, monoalkyl Amino, dialkylamino, alkylsulfanyl, alkenylsulfanyl, or alkynylsulfanyl, more preferred substituents are halogen, alkyl, haloalkyl or alkyloxy, and more preferred substituents are fluoro, chloro, bromo, iodo, methyl, Ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, trifluoromethyl, trichloromethyl, tribromomethyl or triio Particularly preferred substituents are fluoro,
  • R 3 is more preferably a group shown below.
  • R 4 is preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic An aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, and most preferably a hydrogen atom.
  • R 5 is preferably absent, hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted A substituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, particularly preferably absent.
  • R 6 is preferably halogen, cyano, nitro, or —Z 6 —R 61 (Z 6 is a single bond, —O—, —S—, —NR 62 —, —CO—, —CS—, — SO 2 —, —O—CO—, —CO—O—, —NR 62 —CO—, —CO—NR 62 —, —CH 2 —CO—NR 62 —, —NR 63 —CO—NR 62 —, —NR 62 —CS—, —CS—NR 62 —, —NR 63 —CS—NR 62 —, —NR 62 —SO 2 —, —SO 2 —NR 62 —, or —NR 63 —SO 2 —NR 62 -;
  • R 61 represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsub
  • Z 6 is more preferably a single bond, —NR 62 —, —NR 62 —CO—, —CO—NR 62 —, —CH 2 —CO—NR 62 —, —NR 63 —CO—NR.
  • R 61 is preferably a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. Or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably alkyl, and still more preferably methyl.
  • R 62 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom.
  • R 63 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom.
  • R 61 is substituted alkyl, substituted alkenyl, or substituted alkynyl
  • the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred.
  • R 61 is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group
  • the substituent I is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
  • R 6 is more preferably a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclic group. More preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, more preferably substituted or unsubstituted alkyl, and particularly preferably carbon. It is an alkyl having a number of 1 to 4, and most preferably methyl.
  • R 7 is preferably halogen, cyano, nitro, or —Z 7 —R 71 (Z 7 is a single bond, —O—, —S—, —NR 72 —, —CO—, —CS—, — SO 2 —, —O—CO—, —CO—O—, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, -NR 72 -CS -, - CS- NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, - SO 2 -NR 72 - or -NR 73 -SO 2 -NR 72, -;
  • R 71 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alky
  • Z 7 is more preferably a single bond, —O—, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73.
  • R 71 is preferably a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group.
  • a substituted or unsubstituted non-aromatic heterocyclic group more preferably aromatic carbocyclic alkyl, non-aromatic carbocyclic alkyl, aromatic heterocyclic alkyl, non-aromatic heterocyclic alkyl, aromatic carbon A cyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group, more preferably benzyl, phenethyl, cyclohexyl, dihydroindenyl, phenyl, naphthyl, pyridyl, Pyrimidinyl or cycloalkyl, particularly preferably 4-8 membered cycloalkyl.
  • R 72 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, and still more preferably a hydrogen atom or methyl.
  • R 73 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or alkyl, still more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom.
  • R 71 is more preferably a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic carbocyclic group, and further preferably substituted or unsubstituted cycloalkyl or substituted or unsubstituted phenyl.
  • R 71 is substituted alkyl, substituted alkenyl, or substituted alkynyl
  • the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred, and aromatic carbocyclic groups are more preferred.
  • R 71 is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group
  • R 7 is more preferably —Z 7 —R 71 (Z 7 is a single bond, —O—, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO -NR 72 -, - NR 73 -CO -NR 72 -, - NR 73 -CS-NR 72 -, - NR 72 -SO 2 -, or -NR 73 -SO 2 -NR 72 -;
  • R 71 is substituted Or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted non-substituted Aromatic heterocyclic group;
  • R 72 and R 73 are each independently a hydrogen atom or substituted or unsubstituted alkyl, and particularly
  • R 71 is a substituted or unsubstituted aromatic carbocyclic group or a substituted or unsubstituted non-aromatic carbocyclic group;
  • R 72 and R 73 are each independently a hydrogen atom or Non-replaced A kill), and most preferably, -Z 7 -R 71 (Z 7 is -NH-CO-NH-; R 71 is cycloalkyl).
  • R 7 is more preferably a group shown below.
  • R 1 and R 7 together with adjacent carbon atoms are substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocycles, and A cyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed, and a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group is formed.
  • the cyclic group formed by R 1 and R 7 together with adjacent carbon atoms is preferably a 5- to 8-membered non-aromatic heterocyclic group, more preferably a 6-membered ring,
  • the cyclic group may be substituted with a plurality of RA .
  • each R A is preferably independently halogen, cyano, nitro, oxo, or —Z A —R A1 (Z A is a single bond, —O—, —S—, —NR A2 —).
  • R A1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclic group, substituted Or unsubstituted non-aromatic carbocyclic , Substituted or unsubstituted aromatic heteroaryl
  • X is preferably —C (R 10 ) 2 —, —NR 9 —, or —O—, and more preferably —NR 9 —.
  • Y is preferably —C (R 10 ) 2 —, —CO—, or —SO 2 —, more preferably —CH 2 — or —CO—.
  • W is preferably —C (R 10 ) 2 —, —NR 10 —, or —O—, and more preferably —CH 2 —.
  • X is —NR 9 —
  • Y is —CH 2 — or —CO—
  • W is —CH 2 —.
  • R 9 is preferably halogen, cyano, nitro, or —Z 9 —R 91 (Z 9 is a single bond, —O—, —S—, —NR 92 —, —CO—, —CS—, — SO 2 —, —O—CO—, —CO—O—, —NR 92 —CO—, —CO—NR 92 —, —CH 2 —CO—NR 92 —, —NR 93 —CO—NR 92 —, —NR 92 —CS—, —CS—NR 92 —, —NR 93 —CS—NR 92 —, —NR 92 —SO 2 —, —SO 2 —NR 92 —, or —NR 93 —SO 2 —NR 92 -;
  • R 91 represents a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsub
  • a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group may be formed, and more preferably —Z 9 —R 91 .
  • Z 9 is more preferably a single bond, —CO—, —CS—, —SO 2 —, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —.
  • it is —CO—NH—.
  • R 91 is preferably a hydrogen atom, a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, or a substituted or unsubstituted non-aromatic carbocyclic group, more preferably a substituted Or an unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group or a substituted or substituted or unsubstituted non-aromatic carbocyclic group, more preferably methyl, benzyl, phenyl or cycloalkyl, Most preferred is 4-8 membered cycloalkyl.
  • R 92 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom.
  • R 93 is preferably a hydrogen atom or substituted or unsubstituted alkyl, more preferably a hydrogen atom or methyl, and particularly preferably a hydrogen atom.
  • R 91 is substituted alkyl, substituted alkenyl, or substituted alkynyl
  • the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred, and aromatic carbocyclic groups are more preferred.
  • R 91 is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group
  • the substituent I is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
  • R 9 is more preferably —Z 9 —R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —;
  • R 91 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, or substituted or unsubstituted non-aromatic carbocyclic group;
  • R 92 is hydrogen atom or substituted or unsubstituted -Z 9 -R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —).
  • R 91 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, or substituted or unsubstituted non-aromatic heterocyclic group;
  • R 92 is a hydrogen atom), most preferably is, -Z 9 -R 91 Z 9 is -CO-NH-;
  • R 91 is cycloalkyl).
  • R 9 is more preferably a group shown below.
  • R 9 particularly preferably has a cyclic group such as cycloalkyl or phenyl at the terminal.
  • the cyclic group may have a crosslinked structure such as adamantyl.
  • R 10 is each independently preferably a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, more preferably a hydrogen atom or a substituted or unsubstituted Alkyl, more preferably a hydrogen atom.
  • R 10 When R 10 is substituted alkyl, substituted alkenyl, or substituted alkynyl, the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred.
  • R 10 is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group
  • the substituent Is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
  • R 5 and R 7 together with the adjacent nitrogen and carbon atoms may form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group.
  • the cyclic group formed by R 5 and R 7 together with the adjacent nitrogen and carbon atoms is preferably a 5- to 8-membered ring, more preferably a 5- to 6-membered ring, still more preferably a 5-membered ring, , Each may be substituted with a plurality of independent R 8 .
  • the number of R 8 to be substituted is preferably 2 or less, and more preferably 1 or less.
  • the cyclic group preferably contains 1 to 4 nitrogen atoms, and more preferably has one of the following structures (in the formula, the broken line indicates the presence or absence of a bond, provided that the adjacent broken line) Does not indicate the presence of a bond at the same time).
  • the compound of formula (I) is preferably of formula (IV ) To (VI).
  • R 8 is preferably halogen, cyano, nitro, or —Z 8 —R 81 (Z 8 is a single bond, —O—, —S—, —NR 82 —, —CO—, —CS —, —SO 2 —, —O—CO—, —CO—O—, —NR 82 —CO—, —CO—NR 82 —, —CH 2 —CO—NR 82 —, —NR 83 —CO—NR 82 -, - NR 82 -CS - , - CS-NR 82 -, - NR 83 -CS-NR 82 -, - NR 82 -SO 2 -, - SO 2 -NR 82 -, or -NR 83 -SO 2 —NR 82 —;
  • R 81 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkeny
  • substituents are exemplified by halogen, alkyl, haloalkyl, alkoxy and the like.
  • R 81 is substituted alkyl, substituted alkenyl, or substituted alkynyl
  • the substituent is an aromatic carbocyclic group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic group Heterocyclic groups are preferred.
  • R 81 is a substituted aromatic carbocyclic group, a substituted non-aromatic carbocyclic group, a substituted aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group
  • the substituent I is preferably an alkyl, alkenyl, alkynyl, aromatic carbocyclic group, non-aromatic carbocyclic group, aromatic heterocyclic group, or non-aromatic heterocyclic group.
  • R 5 and R 6 may be combined with adjacent nitrogen and carbon atoms to form a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted non-aromatic heterocyclic group.
  • Formula (I) may take the structure shown below.
  • Preferred embodiments of the compound represented by the formula (I) include the following 1) to 4) in the formula (II).
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted aromatic carbocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, — CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 —SO 2 -NR 72 -;
  • R 71 is a substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted non-aromatic carbocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 — SO 2 —NR 72 —;
  • R 71 is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, — CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 —SO 2 -NR 72 -;
  • R 71 is a substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1, and
  • R 3 is a substituted or unsubstituted non-aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is a single bond, —NR 72 —, —NR 72 —CO—, —CO—NR 72 —, —CH 2 —CO—NR 72 —, —NR 73 —CO—NR 72 —, —NR 73 —CS—NR 72 —, —NR 72 —SO 2 —, or —NR 73 — SO 2 —NR 72 —;
  • R 71 is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —CH 2 —, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —CH 2 —, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CH 2 —, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CH 2 —, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is Single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocycle A compound of the formula: R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CH 2 —, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CH 2 —, W is —CH 2 —, R 9 is —Z 9 —R 91 (Z 9 is Single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocycle A compound of the formula: R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —NH—, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —NH—, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —NH—, R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —O—, R 9 is —Z 9 —R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —O—, R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —O—, R 9 is —Z 9 —R 91 (Z 9 is a single bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —CO—, W is —O—, R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —O—, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —O—, and R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —O—, and R 9 is —Z 9 —R 91 (Z 9 is a single bond) , —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 represents a substituted or unsubstituted alkyl or a substituted or unsubstituted aromatic carbocyclic group R 92 is a hydrogen atom).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted non-aromatic heterocyclic group, R 4 is a hydrogen atom, and R 6 is Substituted or unsubstituted alkyl, X is —NR 9 —, Y is —SO 2 —, W is —O—, and R 9 is —Z 9 —R 91 (Z 9 is a single atom) A bond, —CO—, —CO—NR 92 —, —CS—NR 92 —, or —SO 2 —NR 92 —; R 91 is substituted or unsubstituted alkyl or substituted or unsubstituted aromatic carbocyclic A group; R 92 is a hydrogen atom).
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted aromatic carbocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted non-aromatic carbocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted non-aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is substituted or unsubstituted alkyl
  • R 8 is a substituted or unsubstituted aromatic carbocyclic group.
  • R 8 does not exist for the compound of the formula (VI).
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is substituted or unsubstituted aromatic carbocyclic group, substituted or An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is A compound that is substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is —NH—CO—NH—; R 71 is a substituted or unsubstituted aromatic carbocyclic group) .
  • R 1 is substituted or unsubstituted alkyl
  • R 2 is substituted or unsubstituted alkyloxy
  • n is 1
  • R 3 is a substituted or unsubstituted aromatic carbocyclic group, substituted or An unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group
  • R 4 is a hydrogen atom
  • R 6 is A substituted or unsubstituted alkyl
  • R 7 is —Z 7 —R 71 (Z 7 is —NH—CO—NH—; R 71 is a substituted or unsubstituted non-aromatic carbocyclic group).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y and W are both —CH 2 —, and R 9 is —Z 9 —R 91 (Z 9 is —CO—NH—; R 91 is a compound which is a substituted or unsubstituted aromatic carbocyclic group).
  • R 2 is substituted or unsubstituted alkyloxy, n is 1, R 3 is a substituted or unsubstituted aromatic carbocyclic group, R 4 is a hydrogen atom, and R 6 is substituted Or unsubstituted alkyl, X is —NR 9 —, Y and W are both —CH 2 —, and R 9 is —Z 9 —R 91 (Z 9 is —CO—NH—; R 91 is a compound which is a substituted or unsubstituted non-aromatic carbocyclic group).
  • R 4 is a hydrogen atom. It is a point to have.
  • R 7 is represented by the formula (II) in which —Z 7 —R 71 (Z 7 is —NR 73 —CO—NR 72 —; R 71 is a substituted or unsubstituted non-aromatic carbocyclic group)
  • the compound, and X is —NR 9 — and R 9 is —Z 9 —R 91 (Z 9 is —CO—NR 92 —; R 91 is a substituted or unsubstituted non-aromatic carbocyclic group).
  • the compound represented by the formula (III) exhibits a strong HIV replication inhibitory action against resistant viruses. That is, as a preferred embodiment of the compound of the present invention, the presence of a urea structure at R 7 in the formula (II) and X in the formula (III) is important for showing a strong medicinal effect.
  • the compound of formula (I) is not limited to a particular isomer, but all possible isomers (eg keto-enol isomer, imine-enamine isomer, diastereoisomer, atropisomer) , Optical isomers, rotational isomers, etc.), racemates or mixtures thereof.
  • One or more hydrogen, carbon and / or other atoms of the compound of formula (I) may be replaced with isotopes of hydrogen, carbon and / or other atoms, respectively.
  • isotopes are 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 18 O, 17 O, 31 P, 32 P, 35 S, 18 F, 123 I and Like 36 Cl, hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine are included.
  • the compound represented by the formula (I) also includes a compound substituted with such an isotope.
  • the compound substituted with the isotope is useful as a pharmaceutical, and includes all radiolabeled compounds of the compound represented by the formula (I).
  • a “radiolabeling method” for producing the “radiolabeled product” is also encompassed in the present invention, and is useful as a metabolic pharmacokinetic study, a study in a binding assay, and / or a diagnostic tool.
  • the radioactive label of the compound represented by the formula (I) can be prepared by a method well known in the art.
  • the tritium-labeled compound represented by the formula (I) can be prepared by introducing tritium into the specific compound represented by the formula (I) by, for example, catalytic dehalogenation reaction using tritium.
  • a tritium gas is reacted with a precursor in which the compound of formula (I) is appropriately halogen-substituted in the presence of a suitable catalyst such as Pd / C, in the presence or absence of a base.
  • a suitable catalyst such as Pd / C
  • 14 C-labeled compounds can be prepared by using raw materials having 14 C carbon.
  • an alkali metal for example, lithium, sodium, potassium, etc.
  • an alkaline earth metal for example, Calcium, barium, etc.
  • magnesium transition metals (eg, zinc, iron, etc.), ammonia, organic bases (eg, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, diethanolamine, ethylenediamine, pyridine, Picolin, quinoline etc.) and salts with amino acids, or inorganic acids (eg hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, hydrobromic acid, phosphoric acid, hydroiodic acid etc.) and organic acids (eg formic acid, acetic acid, Propionic acid, trifluoroacetic acid, citric acid, lactic acid Tartaric acid, oxalic acid, maleic acid, fum
  • the compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a solvate (for example, a hydrate etc.) and / or a crystalline polymorph.
  • a solvate for example, a hydrate etc.
  • the “solvate” may be coordinated with an arbitrary number of solvent molecules (for example, water molecules) with respect to the compound represented by the formula (I).
  • solvent molecules for example, water molecules
  • the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof When the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof is left in the air, it may absorb moisture and adsorbed water may adhere or form a hydrate.
  • the compound represented by formula (I) or a pharmaceutically acceptable salt thereof may be recrystallized to form a crystalline polymorph thereof.
  • the compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a prodrug, and the present invention includes such various prodrugs.
  • a prodrug is a derivative of a compound of the invention that has a group that can be chemically or metabolically degraded and is a compound that becomes a pharmaceutically active compound of the invention in vivo by solvolysis or under physiological conditions.
  • a prodrug is a compound that is enzymatically oxidized, reduced, hydrolyzed, etc. under physiological conditions in vivo to be converted into a compound represented by formula (I), hydrolyzed by gastric acid, etc. The compound etc. which are converted into the compound shown are included. Methods for selecting and producing suitable prodrug derivatives are described, for example, in Design of Prodrugs, Elsevier, Amsterdam 1985. Prodrugs may themselves have activity.
  • the compound represented by formula (I) or a pharmaceutically acceptable salt thereof has a hydroxyl group
  • prodrugs such as acyloxy derivatives and sulfonyloxy derivatives produced by reacting sulfonyl anhydride and mixed anhydride or by reacting with a condensing agent.
  • CH 3 COO—, C 2 H 5 COO—, t-BuCOO—, C 15 H 31 COO—, PhCOO—, (m-NaOOCPh) COO—, NaOOCCH 2 CH 2 COO—, CH 3 CH (NH 2 ) COO—, CH 2 N (CH 3 ) 2 COO—, CH 3 SO 3 —, CH 3 CH 2 SO 3 —, CF 3 SO 3 —, CH 2 FSO 3 —, CF 3 CH 2 SO 3 —, p —CH 3 —O—PhSO 3 —, PhSO 3 —, and p—CH 3 PhSO 3 — can be mentioned.
  • the compound represented by the formula (I) according to the present invention can be produced, for example, by the general synthesis method shown below. Extraction, purification, and the like may be performed in a normal organic chemistry experiment. The synthesis of the compound of the present invention can be carried out in consideration of techniques known in the art.
  • Step 1 Benzylamine is added to compound a1 in an aqueous solvent and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 hour to 2 hours.
  • compound a2 can be obtained.
  • Second Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and a triflating agent such as trifluoromethanesulfonic anhydride and comin's reagent are added to compound a2.
  • a base such as pyridine, lutidine, triethylamine and a triflating agent such as trifluoromethanesulfonic anhydride and comin's reagent are added to compound a2.
  • Compound a3 can be obtained by reacting at ⁇ 50 ° C. to 50 ° C., preferably ⁇ 30 ° C. to 30 ° C. for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.
  • compound a3 is added with a phosphine such as tritert-butylphosphine, tricyclohexylphosphine, triphenylphosphine, and dibenzylideneacetone palladium, palladium acetate,
  • a catalyst such as dichlorobistriphenylphosphine palladium and silyl enol ether a4 prepared separately from zinc fluoride are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.
  • Compound a5 can be obtained by reacting in 5 to 2 hours. Fourth Step In a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, a brominating agent such as bromine or NBS is added to compound a5, and the temperature is ⁇ 50 ° C. to 50 ° C., preferably ⁇ 30 ° C. to 30 ° C.
  • the compound a6 can be obtained by reacting for 0.1 to 4 hours, preferably 0.5 to 1 hour.
  • Step 5 In a solvent such as DMF, DMA, THF, dioxane, water, or a mixed solvent thereof, an aqueous solution of a base such as potassium carbonate, sodium carbonate, potassium phosphate and boronic acid a7, or boronic ester in compound a6 a8 and a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium and the like are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to Compound a9 can be obtained by reacting for 2 hours.
  • a base such as potassium carbonate, sodium carbonate, potassium phosphate and boronic acid a7, or boronic ester
  • a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphin
  • Step 6 In a solvent such as methanol, ethyl acetate, acetic acid, or a mixed solvent thereof, a catalyst such as palladium carbon, palladium hydroxide, Raney nickel is added to compound a9, and a hydrogen atmosphere is used at 30 ° C. to 130 ° C., preferably Compound a10 can be obtained by reacting at 50 to 110 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours. Seventh Step From compound a10, compound a11 can be obtained in the same manner as in the second step.
  • a catalyst such as palladium carbon, palladium hydroxide, Raney nickel
  • a solvent such as DMF, DMA, THF, or dioxane, or in a mixed solvent thereof, a compound such as triethylamine, lutidine, or pyridine, a base such as triethylamine, benzylamine, and dibenzylideneacetone palladium, palladium acetate, or dichlorobistriphenylphosphine palladium.
  • a ligand such as xanthophos, tri-tert-butylphosphine and the like, and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to 2 hours.
  • compound a13 can be obtained in the same manner as in the second step.
  • Step 10 In a solvent such as dichloroethane, benzene, dioxane or the like or a mixed solvent thereof, a base such as triethylamine, lutidine, pyridine and the isocyanate a14 are added to compound a13, and 50 ° C to 150 ° C, preferably 70 ° C to 130 ° C.
  • the compound A-1 can be obtained by reacting for 0.1 to 8 hours, preferably 0.5 to 2 hours.
  • Step 11 In a solvent such as methanol, THF, dioxane, or a mixed solvent thereof, a base such as an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, or an aqueous lithium hydroxide solution is added to compound A-1 at 10 ° C to 110 ° C.
  • a base such as an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, or an aqueous lithium hydroxide solution is added to compound A-1 at 10 ° C to 110 ° C.
  • Compound A-2 can be obtained by reacting at 30 ° C. to 90 ° C. for 0.1 hour to 8 hours, preferably 0.5 hour to 1 hour.
  • a4 can be synthesized by the following method.
  • Step 12 In a solvent such as THF, diethyl ether, dioxane, or a mixed solvent thereof, compound a15 and an alcohol such as tert-butanol, isopropanol, or methanol, and a metal such as sodium hydride, lithium hydride, or potassium hydride
  • Compound a16 can be obtained by adding a reagent and reacting at 20 ° C. to 120 ° C., preferably 40 ° C. to 100 ° C., for 0.1 hour to 12 hours, preferably 0.5 hour to 6 hours.
  • Step 13 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a16 is mixed with a base such as potassium carbonate, calcium carbonate, potassium phosphate and the like and R 4 -I, R 4 -Br, R 4.
  • a base such as potassium carbonate, calcium carbonate, potassium phosphate and the like and R 4 -I, R 4 -Br, R 4.
  • Step 14 In a solvent such as THF, diethyl ether, dioxane, or a mixed solvent thereof, compound a17 is subjected to silylation with a base such as potassium hexamethyldisilazide, lithium hexamethyldisilazide, or lithium diisopropylamide and TMSCl, TMSOTf or the like.
  • the compound a4 is obtained by adding an agent and reacting at ⁇ 130 ° C. to ⁇ 20 ° C., preferably ⁇ 110 ° C. to ⁇ 50 ° C. for 0.1 hour to 5 hours, preferably 0.5 hour to 1 hour. be able to.
  • Step 1 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound a11 includes a base such as triethylamine or pyridine, an amine b1, dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium, and the like.
  • a catalyst and an inorganic salt such as lithium bromide, sodium bromide and potassium bromide are added, and a carbon monoxide atmosphere is used at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C. for 0.1 hour to 8 hours, preferably Can be obtained by reacting for 0.5 to 2 hours.
  • Second Step From compound B-1, compound B-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • R 2 ′ , R 3 , R 4 and R 91 are as defined above.
  • L 1 is substituted or unsubstituted alkyl, etc.
  • First Step From compound f1, compound f2 can be obtained in the same manner as in the first step in 1) above.
  • Second Step From compound f2, compound f3 can be obtained in the same manner as in the second step in 1) above.
  • Third Step From compound f3, compound f4 can be obtained in the same manner as in the third step in 1) above.
  • Fourth Step From compound f4, compound f5 can be obtained in the same manner as in the fourth step in 1) above.
  • Fifth Step From compound f5, compound f8 can be obtained in the same manner as in the fifth step in 1) above.
  • compound f9 can be obtained in the same manner as in the sixth step in 1) above.
  • compound f10 can be obtained in the same manner as in the seventh step in 1) above.
  • compound f11 can be obtained in the same manner as in the eighth step in 1) above.
  • 9th process From compound f11 compound f12 can be obtained in the same manner as in the fourth step in 1) above.
  • Tenth Step From compound f12, compound f13 can be obtained in the same manner as in the fifth step in 1) above.
  • compound f14 can be obtained in the same manner as in the sixth step in 1) above.
  • compound F-1 can be obtained in the same manner as in the first step in 4) above.
  • Thirteenth Step From compound F-1, compound F-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Second Step In a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and the amine g3 are added to the compound g2, and -30 ° C to 70 ° C, preferably -10 ° C to By reacting at 50 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours, compound G-1 can be obtained.
  • Third Step From compound G-1, compound G-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • First Step From compound f4, compound n1 can be obtained in the same manner as in the sixth step in 1) above.
  • Second Step From compound n1, compound n2 can be obtained in the same manner as in the fourth step in 1) above.
  • Third Step From compound n2, compound n3 can be obtained in the same manner as in the first step in 2) above.
  • Fourth Step From compound n3, compound n4 can be obtained in the same manner as in the seventh step in 1) above.
  • Fifth Step From compound n4, compound n6 can be obtained in the same manner as in the eighth step in 1) above.
  • Sixth Step From compound n6, compound n7 can be obtained in the same manner as in the sixth step in 1) above.
  • compound n8 can be obtained in the same manner as in the first step in 9) above.
  • Step 8 In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and a reagent such as triphosgene, carbonyldiimidazole, diethyl carbonate, etc. are added to compound n8, and -50 ° C to Compound n9 can be obtained by reacting at 50 ° C., preferably ⁇ 30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.
  • compound n10 can be obtained in the same manner as in the fourth step in 1) above.
  • compound N-1 can be obtained in the same manner as in the fifth step in 1) above.
  • compound N-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Step 1 Amide sulfuric acid is added to compound n8 in a pyridine solvent and reacted at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour.
  • compound o1 can be obtained.
  • Second Step From compound o1, compound o2 can be obtained in the same manner as in the fourth step in 1) above.
  • Third Step From compound o2 compound O-2 can be obtained in the same manner as in the fifth step in 1) above.
  • Fourth Step From compound O-1, compound O-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • compound p4 can be obtained in the same manner as in the eighth step in 14) above.
  • compound p6 can be obtained in the same manner as in the fourth step in 1) above.
  • compound P-1 can be obtained in the same manner as in the fifth step in 1) above.
  • compound P-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Second Step In a solvent such as dichloromethane, THF, dichloroethane, or a mixed solvent thereof, a base such as pyridine, lutidine, triethylamine and thionyl chloride are added to compound n8, and -50 ° C to 50 ° C, preferably -30 ° C to By reacting at 30 ° C. for 0.1 hour to 4 hours, preferably 0.5 hour to 1 hour, compound q1 can be obtained.
  • Second Step Ruthenium tetroxide and sodium periodate are added to compound q1 in a mixed solvent such as acetonitrile and water, and the temperature is ⁇ 50 ° C.
  • compound Q-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Step 1 In a solvent such as DMF, DMA, THF, dioxane, or a mixed solvent thereof, compound w1 is added with a phosphine such as tritert-butylphosphine, tricyclohexylphosphine, triphenylphosphine, dibenzylideneacetone palladium, palladium acetate.
  • a catalyst such as dichlorobistriphenylphosphine palladium, zinc fluoride, and compound a4 are added, and the temperature is 50 ° C. to 150 ° C., preferably 70 ° C.
  • Second Step In a solvent such as methanol, ethyl acetate, acetic acid, or a mixed solvent thereof, a catalyst such as palladium carbon, palladium hydroxide, Raney nickel catalyst is added to compound w2, and 30 ° C. to 130 ° C. in a hydrogen atmosphere, preferably Can be obtained by reacting at 50 ° C. to 110 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours.
  • a catalyst such as palladium carbon, palladium hydroxide, Raney nickel catalyst is added to compound w2, and 30 ° C. to 130 ° C. in a hydrogen atmosphere, preferably Can be obtained by reacting at 50 ° C. to 110 ° C. for 0.1 to 8 hours, preferably 0.5 to 2 hours.
  • Second Step A brominating agent such as bromine or NBS is added to compound w3 in a solvent such as dichloromethane, chloroform, dichloroethane, or a mixed solvent thereof, and -50 ° C to 50 ° C, preferably -30 ° C to 30 ° C.
  • the compound w4 can be obtained by reacting for 0.1 to 4 hours, preferably 0.5 to 1 hour.
  • compound w4 is added with an aqueous solution of a base such as potassium carbonate, sodium carbonate, potassium phosphate, boronic acid or boronic acid ester, And a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium and the like at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably 0.5 to 2 Compound W-1 can be obtained by reacting with time.
  • a base such as potassium carbonate, sodium carbonate, potassium phosphate, boronic acid or boronic acid ester
  • a catalyst such as dibenzylideneacetone palladium, palladium acetate, dichlorobistriphenylphosphine palladium and the like at 50 ° C. to 150 ° C., preferably 70 ° C. to 130 ° C., for 0.1 hour to 8 hours, preferably
  • Step 5 Acetic acid and potassium permanganate are added to Compound W-1 in a tert-butanol aqueous solution, and the temperature is ⁇ 50 ° C. to 50 ° C., preferably ⁇ 30 ° C. to 30 ° C., for 0.1 hour to 4 hours, preferably Compound W-3 can be obtained by reacting in 0.5 hour to 1 hour.
  • Compound W-2 can be obtained in the same manner as in the eleventh step in 1) above.
  • Compound W-4 can be obtained from compound W-3 by the same method.
  • the compound of the present invention Since the compound of the present invention has an HIV replication inhibitory action, it is useful as a therapeutic and / or prophylactic agent for viral infections such as AIDS.
  • the compound of the present invention has not only an HIV replication inhibitory action but also a usefulness as a medicine, and preferably has any or all of the following excellent features. a) The inhibitory effect on CYP enzymes (eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.) is weak. b) Good pharmacokinetics such as high bioavailability and moderate clearance. c) High metabolic stability.
  • CYP enzymes eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.
  • CYP3A4 CYP3A4
  • CYP3A4 CYP3A4
  • e) Not mutagenic.
  • f) Low cardiovascular risk.
  • h) It shows a strong medicinal effect against resistant viruses.
  • i) It is difficult to express resistant viruses.
  • Oral administration may be carried out by preparing a commonly used dosage form such as tablets, granules, powders, capsules and the like according to conventional methods.
  • a commonly used dosage form such as tablets, granules, powders, capsules and the like according to conventional methods.
  • parenteral administration any commonly used dosage form such as an injection can be suitably administered. Since the compound of the present invention preferably has high oral absorbability, it can be suitably used as an oral preparation.
  • отное отное отное отное отное о ⁇ ное ком ⁇ онентs such as excipients, binders, disintegrants, lubricants and the like suitable for the dosage form can be mixed with the effective amount of the compound of the present invention as necessary to obtain a pharmaceutical composition.
  • the dosage of the pharmaceutical composition of the present invention is preferably set in consideration of the age, weight, type and degree of disease, route of administration, etc. of the patient. 100 mg / kg / day, preferably in the range of 0.1 to 10 mg / kg / day. In the case of parenteral administration, although it varies greatly depending on the administration route, it is usually 0.005 to 10 mg / kg / day, preferably 0.01 to 1 mg / kg / day. This may be administered once to several times a day.
  • the compound of the present invention is combined with a reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, etc. (hereinafter abbreviated as a concomitant drug) for the purpose of enhancing the action of the compound or reducing the dose of the compound.
  • a concomitant drug for the purpose of enhancing the action of the compound or reducing the dose of the compound.
  • the administration time of the compound of the present invention and the concomitant drug is not limited, and these may be administered to the administration subject at the same time or may be administered with a time difference.
  • the compound of the present invention and the concomitant drug may be administered as two types of preparations containing each active ingredient, or may be administered as a single preparation containing both active ingredients. *
  • the dose of the concomitant drug can be appropriately selected based on the clinically used dose.
  • the compounding ratio of the compound of the present invention and the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptom, combination and the like. For example, when the administration subject is a human, 0.01 to 100 parts by weight of the concomitant drug may be used per 1 part by weight of the compound of the present invention.
  • the compound of the present invention should be used in the field of gene therapy to prevent the spread of retroviral vector infection beyond the target tissue when using a retroviral vector based on HIV or MLV. Can do.
  • the compound of the present invention is administered in advance in the case where the vector is infected with cells in a test tube and then returned to the body, unnecessary infection in the body can be prevented.
  • reverse transcriptase inhibitor examples include AZT, 3TC, didanosine, sarcitabine, sanylvudine, abacavir, tenofovir, emtricitabine, nevirabin, efavirenz, coupleravirin, etravirin, delavirdine and the like.
  • protease inhibitors examples include indinavir, ritonavir, saquinavir, nelfinavir, amprenavir, atanazavir, lopinavir, fosamprenavir, darunavir, atazanavir, branavir, tipranavir and the like.
  • integrase inhibitor examples include raltegravir, elvitegravir, JTK-656, dolutegravir, S-265744 and the like.
  • anti-HIV drugs include, for example, invasion inhibitors such as maraviroc and bicrivirok, and fusion inhibitors such as enfuvirtide, sifuvirtide, and albuvirtide.
  • Example 11 The following compounds were synthesized according to the above examples.
  • R 1 is methyl, R 2 is tert-butyloxy, n is 1, R 4 is a hydrogen atom, and R 6 is methyl.
  • Example 12 According to the above Example, the following compounds can be synthesized.
  • R 3 is any of the following groups.
  • Test Example 1 HIV Replication Inhibition Test HIV (HTLV-IIIB strain) persistently infected human T cell line Molt-4 clone 8 was cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, and the supernatant was filtered to obtain virus titer. was measured and stored at ⁇ 80 ° C.
  • each anti-human immunodeficiency virus active substance was diluted with the above culture medium to a predetermined concentration, and 50 ⁇ L was dispensed into a 96-well microplate.
  • Test Example 2 CYP Inhibition Test O-deethylation of 7-ethoxyresorufin as a typical substrate metabolic reaction of major human CYP5 molecular species (CYP1A2, 2C9, 2C19, 2D6, 3A4) using commercially available pooled human liver microsomes CYP1A2), methyl-hydroxylation of tolbutamide (CYP2C9), 4′-hydroxylation of mephenytoin (CYP2C19), O-demethylation of dextromethorphan (CYP2D6), and hydroxylation of terfenadine (CYP3A4) The degree to which the amount of metabolite produced was inhibited by the compound of the present invention was evaluated.
  • reaction conditions were as follows: substrate, 0.5 ⁇ mol / L ethoxyresorufin (CYP1A2), 100 ⁇ mol / L tolbutamide (CYP2C9), 50 ⁇ mol / L S-mephenytoin (CYP2C19), 5 ⁇ mol / L dextromethorphan (CYP2D6), 1 ⁇ mol / L terfenadine (CYP3A4); reaction time, 15 minutes; reaction temperature, 37 ° C .; enzyme, pooled human liver microsome 0.2 mg protein / mL; compound concentration of the present invention 1, 5, 10, 20 ⁇ mol / L (4 points) .
  • resorufin CYP1A2 metabolite
  • CYP1A2 metabolite resorufin in the centrifugation supernatant was quantified with a fluorescent multi-label counter
  • tolbutamide hydroxide CYP2C9 metabolite
  • mephenytoin 4 ′ hydroxide CYP2C19 metabolite
  • Dextrorphan CYP2D6 metabolite
  • terfenadine alcohol CYP3A4 metabolite
  • CYP3A4 Fluorescence MBI test is a test for examining the enhancement of CYP3A4 inhibition of the compounds of the present invention by metabolic reaction.
  • 7-Benzyloxytrifluoromethylcoumarin (7-BFC) is debenzylated by the CYP3A4 enzyme (E. coli expression enzyme) to produce a fluorescent metabolite 7-hydroxytrifluoromethylcoumarin (7-HFC).
  • CYP3A4 inhibition was evaluated using 7-HFC production reaction as an index.
  • reaction conditions are as follows: substrate, 5.6 ⁇ mol / L 7-BFC; pre-reaction time, 0 or 30 minutes; reaction time, 15 minutes; reaction temperature, 25 ° C. (room temperature); CYP3A4 content (E. coli expression enzyme), Pre-reaction 62.5 pmol / mL, reaction 6.25 pmol / mL (10-fold dilution); compound concentration of the present invention, 0.625, 1.25, 2.5, 5, 10, 20 ⁇ mol / L (6 points) ).
  • the enzyme and the compound solution of the present invention are added to the 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) in the above-mentioned pre-reaction composition, and the substrate and K-Pi buffer are added to another 96-well plate.
  • a part of the solution was transferred so as to be diluted by 1/10, and a reaction using NADPH as a coenzyme was started as an indicator (no pre-reaction).
  • NADPH is also added to the remaining pre-reaction solution to start the pre-reaction (pre-reaction is present), and after pre-reaction for a predetermined time, one plate is diluted to 1/10 with the substrate and K-Pi buffer.
  • a control (100%) was obtained by adding only DMSO, which is a solvent in which the compound of the present invention was dissolved, to the reaction system, and the residual activity (%) when each concentration of the compound of the present invention was added was calculated.
  • DMSO a solvent in which the compound of the present invention was dissolved
  • Test Example 4 Metabolic Stability Test A commercially available pooled human liver microsome and the compound of the present invention were reacted for a certain period of time, and the residual rate was calculated by comparing the reaction sample with the unreacted sample to evaluate the degree of metabolism of the compound of the present invention in the liver. .
  • the compound of the present invention in the centrifugal supernatant was quantified by LC / MS / MS, and the residual amount of the compound of the present invention after the reaction was calculated with the compound amount at 0 minute reaction as 100%.
  • the hydrolysis reaction was carried out in the absence of NADPH, and the glucuronic acid conjugation reaction was carried out in the presence of 5 mmol / L UDP-glucuronic acid instead of NADPH, and thereafter the same operation was carried out.
  • Micro F buffer K 2 HPO 4 : 3.5 g / L, KH 2 PO 4 : 1 g / L, (NH 4 ) 2 SO 4 : 1 g / L, trisodium citrate dihydrate: 0.
  • MicroF containing 110 mL Exposure medium Biotin: 8 ⁇ g / mL, Histidine: 0.2 ⁇ g / mL, Glucose: 8 mg / mL) suspended in 25 g / L, MgSO 4 ⁇ 7H 2 0: 0.1 g / L) Buffer).
  • the TA100 strain was added to 120 mL of Exposure medium with respect to the 3.16 mL bacterial solution to prepare a test bacterial solution.
  • Compound DMSO solution of the present invention (maximum dose of 50 mg / mL to several-fold dilution at 2-3 times common ratio), DMSO as a negative control, and non-metabolic activation conditions as a positive control, 50 ⁇ g / mL 4-TA Nitroquinoline-1-oxide DMSO solution, 0.25 ⁇ g / mL 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide DMSO solution for TA100 strain, TA98 under metabolic activation conditions 40 ⁇ g / mL 2-aminoanthracene DMSO solution for the strain and 20 ⁇ g / mL 2-aminoanthracene DMSO solution for the TA100 strain, respectively, and 588 ⁇ L of the test bacterial solution (498 ⁇ L of the test bacterial solution and S9 under metabolic activation conditions).
  • Intravenous administration is performed from the tail vein using a syringe with a needle.
  • Evaluation item Blood is collected over time, and the concentration of the compound of the present invention in plasma is measured using LC / MS / MS.
  • Statistical analysis The plasma concentration-time curve area (AUC) is calculated using the non-linear least squares program WinNonlin (registered trademark) for the plasma concentration of the compound of the present invention, and the oral administration group and intravenous administration
  • the bioavailability (BA) of the compound of the present invention is calculated from the AUC of the group.
  • HEK293 cells expressing a human ether-a-go-go related gene (hERG) channel were used and important for the ventricular repolarization process.
  • the effect of the compounds of the present invention on the delayed rectifier K + current (I Kr ) playing a role was investigated.
  • a fully automatic patch clamp system PatchXpress 7000A, Axon Instruments Inc.
  • a +40 mV depolarization stimulus was applied for 2 seconds, followed by a ⁇ 50 mV repolarization.
  • the absolute value of the maximum tail current was measured using the analysis software (DataXpress ver. 1, Molecular Devices Corporation) based on the current value at the holding membrane potential. Furthermore, the inhibition rate with respect to the maximum tail current before application of the compound of the present invention was calculated, and compared with the vehicle application group (0.1% dimethyl sulfoxide solution), the effect of the compound of the present invention on I Kr was evaluated.
  • the compound of the present invention was quantified using HPLC by an absolute calibration curve method.
  • Formulation Example 1 Tablet 15 mg of the present compound Lactose 15mg Calcium stearate 3mg Ingredients other than calcium stearate are uniformly mixed, crushed and granulated, and dried to obtain granules of an appropriate size. Next, calcium stearate is added and compressed to form tablets.
  • Formulation Example 2 Capsule Compound of the present invention 10 mg Magnesium stearate 10mg Lactose 80mg Are mixed uniformly to make a powder as a fine powder or powder. It is filled into a capsule container to form a capsule.
  • Formulation Example 3 Granules Compound of the present invention 30 g Lactose 265g Magnesium stearate 5g After mixing well, compression molding, pulverizing, sizing, and sieving to make granules of appropriate size.
  • the compound according to the present invention can be a useful drug as a therapeutic agent for viral infections such as AIDS.

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Abstract

L'invention concerne : un nouveau composé représenté par la formule (I) (dans laquelle une ligne en pointillés représente la présence ou l'absence d'une liaison ; R1 représente un groupe alkyle substitué ou non substitué ou similaire ; R2 représente un groupe alkyloxy substitué ou non substitué ou similaire ; n représente 1 ou 2 ; R3 représente un groupe carbocyclique aromatique substitué ou non substitué ou similaire ; R4 représente un atome d'hydrogène ou similaire ; R5 n'est pas présent ou similaire ; R6 représente un groupe alkyle substitué ou non substitué ou similaire ; R7 représente -Z7-R71 ou similaire ; Z7 représente -NR73-CO-NR72- ou similaire ; R71 représente un groupe carbocyclique aromatique substitué ou non substitué ou similaire ; R72 représente un atome d'hydrogène ou similaire ; et R73 représente un atome d'hydrogène ou similaire), qui a une activité antivirale, en particulier une activité inhibitrice de la réplication du VIH ; et un agent médicinal, en particulier un médicament anti-VIH, qui comprend le composé.
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WO2014119636A1 (fr) 2013-01-31 2014-08-07 塩野義製薬株式会社 Inhibiteur de la réplication du vih
US8987250B2 (en) 2012-04-20 2015-03-24 Gilead Sciences, Inc. Therapeutic compounds
US9006229B2 (en) 2011-04-21 2015-04-14 Gilead Sciences, Inc. Benzothiazole compounds and their pharmaceutical use
US9102614B2 (en) 2010-07-02 2015-08-11 Gilead Sciences, Inc. Naphth-2-ylacetic acid derivatives to treat AIDS
WO2015126765A1 (fr) * 2014-02-19 2015-08-27 Bristol-Myers Squibb Company Inhibiteurs de la réplication du virus de l'immunodéficience humaine
WO2015174511A1 (fr) * 2014-05-16 2015-11-19 塩野義製薬株式会社 Dérivé hétérocyclique tricyclique présentant un effet d'inhibition de la réplication du vih
US9284323B2 (en) 2012-01-04 2016-03-15 Gilead Sciences, Inc. Naphthalene acetic acid derivatives against HIV infection
US9296758B2 (en) 2010-07-02 2016-03-29 Gilead Sciences, Inc. 2-quinolinyl-acetic acid derivatives as HIV antiviral compounds
US9376392B2 (en) 2012-01-04 2016-06-28 Gilead Sciences, Inc. 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS
WO2017029631A1 (fr) * 2015-08-20 2017-02-23 VIIV Healthcare UK (No.5) Limited Dérivés de l'acide pyridin-3-yl-acétique utilisés comme inhibiteurs de la réplication du virus de l'immunodéficience humaine
US10494380B2 (en) 2015-05-29 2019-12-03 Shionogi & Co., Ltd. Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity
US20210371388A1 (en) * 2020-05-12 2021-12-02 Baruch S. Blumberg Institute Bicyclic Carboxamide with Exocyclic Urea Derivatives as Antivirals for the Treatment of HBV Infection

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US9296758B2 (en) 2010-07-02 2016-03-29 Gilead Sciences, Inc. 2-quinolinyl-acetic acid derivatives as HIV antiviral compounds
US9102614B2 (en) 2010-07-02 2015-08-11 Gilead Sciences, Inc. Naphth-2-ylacetic acid derivatives to treat AIDS
US9006229B2 (en) 2011-04-21 2015-04-14 Gilead Sciences, Inc. Benzothiazole compounds and their pharmaceutical use
US9376392B2 (en) 2012-01-04 2016-06-28 Gilead Sciences, Inc. 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS
US9284323B2 (en) 2012-01-04 2016-03-15 Gilead Sciences, Inc. Naphthalene acetic acid derivatives against HIV infection
US8987250B2 (en) 2012-04-20 2015-03-24 Gilead Sciences, Inc. Therapeutic compounds
US9096586B2 (en) 2012-04-20 2015-08-04 Gilead Sciences, Inc. Therapeutic compounds
US20180362543A1 (en) * 2013-01-31 2018-12-20 Shionogi & Co., Ltd. Hiv replication inhibitor
WO2014119636A1 (fr) 2013-01-31 2014-08-07 塩野義製薬株式会社 Inhibiteur de la réplication du vih
US9938271B2 (en) 2014-02-19 2018-04-10 VIIV Healthcare UK (No.5) Limited Inhibitors of human immunodeficiency virus replication
WO2015126765A1 (fr) * 2014-02-19 2015-08-27 Bristol-Myers Squibb Company Inhibiteurs de la réplication du virus de l'immunodéficience humaine
US9975906B2 (en) 2014-05-16 2018-05-22 Shionogi & Co., Ltd. Tricyclic heterocycle derivatives having HIV replication inhibitory effect
JPWO2015174511A1 (ja) * 2014-05-16 2017-04-20 塩野義製薬株式会社 Ｈｉｖ複製阻害作用を有する３環性複素環誘導体
WO2015174511A1 (fr) * 2014-05-16 2015-11-19 塩野義製薬株式会社 Dérivé hétérocyclique tricyclique présentant un effet d'inhibition de la réplication du vih
US10494380B2 (en) 2015-05-29 2019-12-03 Shionogi & Co., Ltd. Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity
US10870661B2 (en) 2015-05-29 2020-12-22 Shionogi & Co., Ltd. Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity
WO2017029631A1 (fr) * 2015-08-20 2017-02-23 VIIV Healthcare UK (No.5) Limited Dérivés de l'acide pyridin-3-yl-acétique utilisés comme inhibiteurs de la réplication du virus de l'immunodéficience humaine
US10106504B2 (en) 2015-08-20 2018-10-23 VIIV Healthcare UK (No.5) Limited Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication
US20210371388A1 (en) * 2020-05-12 2021-12-02 Baruch S. Blumberg Institute Bicyclic Carboxamide with Exocyclic Urea Derivatives as Antivirals for the Treatment of HBV Infection

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