JPS61158989A - Organogermanium compound - Google Patents
Organogermanium compoundInfo
- Publication number
- JPS61158989A JPS61158989A JP59281001A JP28100184A JPS61158989A JP S61158989 A JPS61158989 A JP S61158989A JP 59281001 A JP59281001 A JP 59281001A JP 28100184 A JP28100184 A JP 28100184A JP S61158989 A JPS61158989 A JP S61158989A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- present
- germanium
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 Organogermanium compound Chemical class 0.000 title abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 38
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 abstract description 9
- 229910052732 germanium Inorganic materials 0.000 abstract description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 229940093626 germanium sesquioxide Drugs 0.000 abstract description 2
- 102000035195 Peptidases Human genes 0.000 abstract 1
- 108091005804 Peptidases Proteins 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 235000019833 protease Nutrition 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 150000002291 germanium compounds Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102000001490 Opioid Peptides Human genes 0.000 description 3
- 108010093625 Opioid Peptides Proteins 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003399 opiate peptide Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 235000001270 Allium sibiricum Nutrition 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000005704 oxymethylene group Chemical group [H]C([H])([*:2])O[*:1] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は新規な有機ゲルマニウム化合物に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel organogermanium compound.
金属の一種であるゲルマニウムＧｅは、半導体として旧
くから研究の対象になっていたものであるが、最近にな
ってその有機化合物に関する研究が進んで研究成果の発
表が活発に行なわれるようになった結果、ゲルマニウム
、とりわけその有機化合物は種々の技術分野から注目さ
れるようになった。Germanium Ge, a type of metal, has long been the subject of research as a semiconductor, but recently research into its organic compounds has progressed and research results have been actively published. As a result, germanium, especially its organic compounds, has attracted attention from various technical fields.
例えば、式
％式％
で表わされるカルボキシエチルゲルマニウムセスキオキ
サイドという化合物が、極めて強力な血圧降下作用や抗
腫瘍作用等の生理活性を示す半面。For example, the compound carboxyethyl germanium sesquioxide, represented by the formula %, exhibits extremely strong physiological activities such as blood pressure lowering effects and antitumor effects.
全く毒性や副作用が覚られないものであることは医薬学
会では周知の事実となっているし、本発明の発明者らの
一部も、自己の研究の一環として、一般式
で表わされるユニークなアトラン骨格を有し、強力な抗
菌作用を発揮する有機ゲルマニウム化合物の発明を完成
し、すでに特許出願済みである（特公昭５９−４３４７
９号公報参照）。It is a well-known fact in the medical sciences that there are no toxicity or side effects, and some of the inventors of the present invention also developed a unique compound expressed by the general formula as part of their own research. Completed the invention of an organic germanium compound that has an atlan skeleton and exhibits a strong antibacterial effect, and has already applied for a patent (Japanese Patent Publication No. 59-4347
(See Publication No. 9).
而して、前記化合物■の発揮する血圧降下作用や化合物
■の発揮する抗菌作用のメカニズムは未だ明確には解明
されてはいないが、例えば前者に関しては、その薬理作
用はゲルマニウム−酸素結合に由来するとの説が一部の
研究者により唱えられているので、ゲルマニウムと、酸
素の同族体との結合を含む新規な化合物を合成すること
ができれば、当該化合物は上述した公知化合物に勝ると
も劣らない優れた薬理作用を発揮することが期待される
。Although the mechanisms of the hypotensive effect exerted by compound (1) and the antibacterial effect exerted by compound (2) have not yet been clearly elucidated, for example, the pharmacological effect of the former is derived from the germanium-oxygen bond. Some researchers have advocated the theory that, if a new compound containing a bond between germanium and an oxygen homolog could be synthesized, the compound would be superior to the known compounds mentioned above. It is expected to exhibit excellent pharmacological effects.
本発明は上述した事情を背景として、新規且つ有用な有
機ゲルマニウム化合物を提供することを目的としてなさ
れたもので、その構成は、一般式（式中、Ｒ＋、Ｒｚ、
Ｒａは水素原子又はメチル基、エチル基等の低級アルキ
ル基若しくは置換或いは無置換のフェニル基を、Ｙは水
酸基、アミノ基又は〇−低級アルキル基をそれぞれ表わ
す）で表わされることを特徴とするものである。The present invention was made with the purpose of providing a novel and useful organic germanium compound against the background of the above-mentioned circumstances.
Ra is a hydrogen atom or a lower alkyl group such as a methyl group or an ethyl group, or a substituted or unsubstituted phenyl group, and Y is a hydroxyl group, an amino group, or a 〇-lower alkyl group. It is.
以下に本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の化合物は、７１〜ラン骨格に、置換基Ｒ乃至Ｒ
及び酸素官能基ＣＯＹを有するプロピオン酸残基が結合
したものであって、上述した公知化合物■では、アトラ
ン骨格が窒素原子とゲルマニウム原子とが３本のオキシ
メチレン鎖で架橋されたものであったが、本発明化合物
に於けるアトラン骨格は、窒素原子とゲルマニウム原子
とが３本のチオメチレン鎖で架橋されているもので、そ
□れらチオメチレン鎖の内部を通って窒素の孤立
電子対がゲルマニウム原子に配位した構造をとることを
特色としている。The compound of the present invention has substituents R to R on the 71-ran skeleton.
and a propionic acid residue having an oxygen functional group COY, and in the above-mentioned known compound (2), the atran skeleton was a nitrogen atom and a germanium atom cross-linked with three oxymethylene chains. However, in the atran skeleton in the compound of the present invention, a nitrogen atom and a germanium atom are cross-linked with three thiomethylene chains, and the lone electron pair of nitrogen passes through the inside of these thiomethylene chains to form germanium atoms. It is characterized by a structure that is coordinated with atoms.
ここで、式（Ｉ）中の置換基Ｒｌ、 Ｒ１、ＲＢは水素
原子又はメチル基、エチル基又はプロピル基等の低級ア
ルキル基若しくは置換され或いは無置換のフェニル基を
、酸素官能基中の置換基Ｙは水酸基。Here, the substituents R1, R1, and RB in formula (I) are a hydrogen atom, a lower alkyl group such as a methyl group, an ethyl group, or a propyl group, or a substituted or unsubstituted phenyl group, and a substituent in an oxygen functional group. The group Y is a hydroxyl group.
アミノ基又は〇−低級アルキル基をそれぞれ表わしてお
り、従って、本発明の有機ゲルマニウム化合物は、例え
ば以下に示すような化合物により代表される。Each represents an amino group or a 〇-lower alkyl group. Therefore, the organic germanium compounds of the present invention are typified by, for example, the compounds shown below.
しｌｌｑ ＋、、ｔｉＢ
「−一一一一−１
Ｎ（ＣＨ２，ＣＨｌＳ）Ａ ＧｅＣＨｚＣＨｚＣＯＯＣ
ｌｌａ −−（Ｉ ｉ）このような構造の本発明化合物
は種々の方法により合成することができるが、例えば下
記反応式１に示すように、前記化合物■と同様のゲルマ
ニウムセスキオキサイド（Ｉｌａ）又はその酸素原子を
硫黄原子で置換したゲルマニウムセスキスルフィド（ｎ
ｂ）に、適宜の溶媒中でトリチオエタノールアミン（ｍ
）を反応させれば良いのである。shillq +,,tiB "-1111-1 N(CH2,CHlS)A GeCHzCHzCOOC
lla --(I i) The compound of the present invention having such a structure can be synthesized by various methods. For example, as shown in Reaction Formula 1 below, germanium sesquioxide (Ila) similar to the above compound (I) or Germanium sesquisulfide (n
b), trithioethanolamine (m
) can be reacted.
反応式１
％式％（）
尚、上記反応式中のＺは酸素原子又は硫黄原子を表わし
ている。Reaction Formula 1 %Formula %( ) In the above reaction formula, Z represents an oxygen atom or a sulfur atom.
又、本発明化合物は、前記した特許公報に記載された合
成方法に倣い、下記反応式２に示すように、トロハロゲ
ノゲルミルプロピオン酸誘導体（ＩＶ）にアルコキサイ
ドを作用させて−Ｈトリアルコキシ体（Ｖ）とし、これ
にトリチオエタノールアミン（ｍ）を反応させて合成す
るようにしても良い。In addition, the compound of the present invention can be prepared by reacting an alkoxide with a trohalogenogermylpropionic acid derivative (IV) to form an -H trialkoxy compound, following the synthesis method described in the above-mentioned patent publication, as shown in Reaction Formula 2 below. (V) and may be synthesized by reacting this with trithioethanolamine (m).
反応式２
％式％（１）
更には、下記反応式３に示すように、トリハロゲノゲル
ミルプロピオン酸誘導体（ＩＶ）に、トリチオエタノー
ルアミンのアルカリ金属塩（Ｈａ）やトリメチルシリル
誘導体（■ｂ）を反応させたりしても、本発明化合物を
合成することができる。Reaction formula 2 % formula % (1) Furthermore, as shown in reaction formula 3 below, the trihalogenogermylpropionic acid derivative (IV) is added with an alkali metal salt of trithioethanolamine (Ha) or a trimethylsilyl derivative (■ b ) can also be used to synthesize the compound of the present invention.
反応式３
％式％（）
以上のようにして得られた本発明化合物はいずれも無色
の結晶であって、元素分析（Ｅ Ａ）や質量分析（ＭＡ
ＳＳ）の結果及び核磁気共鳴吸収（ＮＭＲ）スペクトル
や赤外線吸収（ＩＲ）スペクトルの結果は、すべて合成
した化合物が一般式（１）で表わされるべきものである
ことを良く支持するものであった。Reaction formula 3 %Formula %() All of the compounds of the present invention obtained as described above are colorless crystals, and cannot be analyzed by elemental analysis (EA) or mass spectrometry (MA).
The results of SS), nuclear magnetic resonance absorption (NMR) spectrum, and infrared absorption (IR) spectrum all strongly supported that the synthesized compound should be represented by general formula (1). .
而して、本発明の有機ゲルマニウム化合物は。 Thus, the organic germanium compound of the present invention is.
そのアトラン骨格中に３つのゲルマニウム−硫黄結合を
有しているので、冒頭で述べた公知化合物に勝るとも劣
らない優れた薬理作用を発揮することが期待される。Since it has three germanium-sulfur bonds in its atran skeleton, it is expected to exhibit excellent pharmacological effects comparable to those of the known compounds mentioned at the beginning.
事実、本発明化合物を、オピオイドと総称されるペプタ
イド（モルヒネ等の投与により生体内に遊離し当該生体
の自己鎮痛作用を営むとされている）を分解してしまう
オピオイド分解酵素に対し作用させてみると１本発明化
合物は、極めて低い濃度であっても、しかも特定のオピ
オイド分解酵素について、強力な阻害作用を示した。In fact, the compound of the present invention is made to act on an opioid-degrading enzyme that degrades peptides collectively called opioids (which are released into the body upon administration of morphine, etc., and are said to exert a self-analgesic effect in the body). As a result, one compound of the present invention showed a strong inhibitory effect on a specific opioid degrading enzyme even at an extremely low concentration.
従って、本発明化合物は、投与されるモルヒネ等の生体
内での有効利用を図ると共に耽溺性の強いモルヒネ等の
投与量を減するためのオピオイド分解酵素阻害剤として
使用することができるものである。Therefore, the compound of the present invention can be used as an opioid degrading enzyme inhibitor to effectively utilize administered morphine, etc. in the body, and to reduce the dose of morphine, etc., which is highly addictive. .
４−１１．−Ｊ’講”−：Ｉ−Ｐ≦−Ｉ「ノｈメＩＩＩ
＝７−ｒ’５ノ、→ツフうニラ１う二÷トイド５ ｇ
（０，０１４７１１１ｏｌ）にトリチオエタノールアミ
ン５．８ ｇ （０，０３ｎ＋ｏｌ）を加え、ベンゼン
中で５時間加熱還流した。4-11. -J'ko"-:I-P≦-I"Nohme III
= 7-r'5ノ, → Tsufuu chive 1 eel ÷ toid 5 g
5.8 g (0.03 n+ol) of trithioethanolamine was added to (0.0147111 ol), and the mixture was heated under reflux in benzene for 5 hours.
反応終了後、析出する結晶を濾取し、メタノール−エー
テルから再結晶すると、収率５１％で化合物（Ｉ ａ）
を得た。After the reaction, the precipitated crystals were collected by filtration and recrystallized from methanol-ether to give compound (I a) in a yield of 51%.
I got it.
他の本発明化合物も上記と略同様の合成操作により得る
ことができた。Other compounds of the present invention could also be obtained by substantially the same synthetic procedures as above.
ｂＪｄ式１によるヒム Ｉｈのムゝ〈ヒム物ｎｂから〉
１−フェニル−２−カルボキサミドエチルゲルマニウム
セスキスルファイド１．６６ ｇ （３ｍｍｏｌ）とト
リチオエタノールアミン１．２２ ｇ （６ｍｍｏｌ）
とを、１００ｏ１のコルベン中で３０耐のベンゼンを溶
媒として６時間加熱還流した。Him by bJd formula 1 Ih's muゝ〈from Him thing nb〉
1-phenyl-2-carboxamidoethyl germanium sesquisulfide 1.66 g (3 mmol) and trithioethanolamine 1.22 g (6 mmol)
were heated under reflux for 6 hours in 100o1 Kolben using 30 proof benzene as a solvent.
反応終了後、析出する結晶を濾取し、再結晶すると、収
率７０％で化合物（ｔｈ）を得た。After the reaction was completed, the precipitated crystals were collected by filtration and recrystallized to obtain compound (th) in a yield of 70%.
他の本発明化合物も上記と略同様の合成操作により得る
ことができた。Other compounds of the present invention could also be obtained by substantially the same synthetic procedures as above.
Ｃ６式２による ム Ｉｉのム
トリクロルゲルミルプロピオン酸メチルエスチル２．０
ｇ （７，６ｍｍｏｌ）をメタノール１０耐に溶解し
、これに金属ナトリウムから要時調製したナトリウムメ
チラート溶液５０耐を加えると、やや発熱し、塩化ナト
リウムが析出した。Methyl ethyl chlorogermylpropionate of Mu Ii according to C6 formula 2 2.0
g (7.6 mmol) was dissolved in 10 ml of methanol, and when 50 ml of sodium methylate solution prepared from sodium metal was added thereto, a slight heat was generated and sodium chloride precipitated.
反応終了後、塩化ナトリウムを濾過し、濾液にトリチオ
エタノールアミン１．５ ｇ （７，６ｎ＋ｍｏｌ）を
クロロホルム３０ｎ＋１に溶解した溶液を一３０℃で徐
々に加えた後、室温で約１時間攪拌し、続いて２時間加
熱還流した。After the reaction, the sodium chloride was filtered off, and a solution of 1.5 g (7.6 n+mol) of trithioethanolamine dissolved in 30n+1 chloroform was gradually added to the filtrate at -30°C, followed by stirring at room temperature for about 1 hour. , followed by heating under reflux for 2 hours.
反応終了後、溶媒を留去するとオイル状物質が残ったが
、後にこれは結晶化したので、再結晶に付すと、６１％
の収率で化合物（ｒ ｉ）を得た。After the reaction was completed, the solvent was distilled off and an oily substance remained, which later crystallized, so when it was recrystallized, 61%
Compound (r i) was obtained in a yield of .
他の本発明化合物も上記と略同様の合成操作により得る
ことができた。Other compounds of the present invention could also be obtained by substantially the same synthetic procedures as above.
ｄ、−日 ヒム の 理ヒバ１′・データ以上のように
、本発明化合物は種々の方法により合成することができ
、得られた本発明化合物は次の表に例示するような物理
化学的データを示した。d, -day Him's Rihiba 1' Data As mentioned above, the compounds of the present invention can be synthesized by various methods, and the obtained compounds of the present invention have physicochemical data as illustrated in the following table. showed that.
２、、ｔＵＩ＋ １１に玄マニウム化合物の薬理作現在
では多種類のオピオイドベプタイド及び対応するオピオ
イドペプタイド分解酵素が発見されているので、本発明
化合物の薬理活性はオピオイドペプタイド分解酵素の阻
害効果を１ｎＶｉＰ、ｒｏで検定することとした。2. Pharmacological development of brown manium compounds in tUI+ 11 Currently, many types of opioid peptides and corresponding opioid peptide-degrading enzymes have been discovered. It was decided to test with 1nViP, ro.
即ち１本発明化合物の存在下でオピオイドペプタイド又
はそのモデル化合物にオピオイドペプタイド分解酵素を
作用させ１本発明化合物の阻害効果を測定したのであり
、この結果、下記の表に示すように本発明化合物は低濃
度であってもオピオイドペプタイド分解酵素の作用を良
く阻害し、しかも、今回使用したオピオイドペプタイド
分解酵素に関しては、モルモット由来のアンジオテンシ
ン変換酵素のみを阻害し、つまり選択性を有しているこ
とが明らかとなったのである。Specifically, in the presence of the compound of the present invention, an opioid peptide degrading enzyme was allowed to act on an opioid peptide or its model compound, and the inhibitory effect of the compound of the present invention was measured.As shown in the table below, the compound of the present invention It effectively inhibits the action of opioid peptide-degrading enzymes even at low concentrations, and the opioid peptide-degrading enzyme used this time only inhibits guinea pig-derived angiotensin-converting enzyme, indicating that it is selective. It became clear.
表
尚、１掲の表中の数値は本発明化合物を１ｍｇ／＋ｉｌ
の濃度で使用した場合の阻止率を％で表示したものであ
り、又、ＡＰはアミノペプチデース、ＤＰＰはジペプチ
ジルアミノペプチデース。In addition, the numerical values in the table listed above are 1 mg/+il of the compound of the present invention.
The inhibition rate is expressed in % when used at a concentration of , and AP is aminopeptide and DPP is dipeptidyl aminopeptide.
ＡＣＥはアンジオテンシン変換酵素をそれぞれ表わして
いる。ACE stands for angiotensin converting enzyme, respectively.
更に、化合物（Ｉａ）について５０％阻止率（ＩＣ５０
）を算出してみると、２５０μｇ ／ｍｌと良好な値で
あった。Furthermore, 50% inhibition rate (IC50) for compound (Ia)
) was calculated and found to be a good value of 250 μg/ml.
本発明は以上の通りであるから、有機ゲルマニウム化合
物として産業上の利用性大なるものがある。Since the present invention is as described above, it has great industrial applicability as an organic germanium compound.
Claims (1)
。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. , Y represents a hydroxyl group, an amino group, or an O-lower alkyl group, respectively.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59281001A JPS61158989A (en) | 1984-12-29 | 1984-12-29 | Organogermanium compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59281001A JPS61158989A (en) | 1984-12-29 | 1984-12-29 | Organogermanium compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61158989A true JPS61158989A (en) | 1986-07-18 |
| JPS6332359B2 JPS6332359B2 (en) | 1988-06-29 |
Family
ID=17632883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59281001A Granted JPS61158989A (en) | 1984-12-29 | 1984-12-29 | Organogermanium compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61158989A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0548230U (en) * | 1991-11-29 | 1993-06-25 | 第一電子工業株式会社 | Surface mount connector |
| US6451850B1 (en) | 1998-08-17 | 2002-09-17 | Evgeny Vladimirovich Soloviev | Bio-chemical germanium complexes with high therapeutic efficiency and wide application spectrum |
-
1984
- 1984-12-29 JP JP59281001A patent/JPS61158989A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0548230U (en) * | 1991-11-29 | 1993-06-25 | 第一電子工業株式会社 | Surface mount connector |
| US6451850B1 (en) | 1998-08-17 | 2002-09-17 | Evgeny Vladimirovich Soloviev | Bio-chemical germanium complexes with high therapeutic efficiency and wide application spectrum |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6332359B2 (en) | 1988-06-29 |
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