JPH0583558B2 - - Google Patents
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- Publication number
- JPH0583558B2 JPH0583558B2 JP60271750A JP27175085A JPH0583558B2 JP H0583558 B2 JPH0583558 B2 JP H0583558B2 JP 60271750 A JP60271750 A JP 60271750A JP 27175085 A JP27175085 A JP 27175085A JP H0583558 B2 JPH0583558 B2 JP H0583558B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- present
- compounds
- germanium
- formula
- 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.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 150000002291 germanium compounds Chemical class 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
- 102000001490 Opioid Peptides Human genes 0.000 description 5
- 108010093625 Opioid Peptides Proteins 0.000 description 5
- 229910052732 germanium Inorganic materials 0.000 description 5
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- 239000003399 opiate peptide Substances 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000593 degrading effect Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- XEABSBMNTNXEJM-UHFFFAOYSA-N propagermanium Chemical compound OC(=O)CC[Ge](=O)O[Ge](=O)CCC(O)=O XEABSBMNTNXEJM-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 102000004400 Aminopeptidases Human genes 0.000 description 2
- 108090000915 Aminopeptidases Proteins 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000457 gamma-lactone group Chemical group 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 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 1
- NLIJOIUVZBYQRS-UHFFFAOYSA-N 3-trichlorogermylpropanoic acid Chemical compound OC(=O)CC[Ge](Cl)(Cl)Cl NLIJOIUVZBYQRS-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- WOPFYEBXNBBNKV-UHFFFAOYSA-N O[GeH2]C(C)C(O)=O Chemical class O[GeH2]C(C)C(O)=O WOPFYEBXNBBNKV-UHFFFAOYSA-N 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HCXOEFUEXIXLCL-UHFFFAOYSA-N [Br].[Ge] Chemical compound [Br].[Ge] HCXOEFUEXIXLCL-UHFFFAOYSA-N 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 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
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- -1 organogermanium compound Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 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
- 238000010992 reflux Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
〔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。
〔従来の技術〕
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つていたものであ
るが、最近になつ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
になつた結果、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
つた。
例えば、式（GeCH2CH2COOH）2O3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、全く毒性
や副作用が見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つている如くである。
〔発明が解決しようとする問題点〕
而して、前記カルボキシエチルゲルマニウムセ
スキオキサイドの発揮する血圧降下作用や抗腫瘍
作用等のメカニズムは未だ明確には解明されては
いないが、一部の研究者により、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唱え
られているので、網目状で且つシート状の化合物
である前記カルボキシエチルゲルマニウムセスキ
オキサイドにおけるものとは異つた種類のゲルマ
ニウム−酸素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。
〔問題点を解決するための手段〕
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
[Industrial Application Field] The present invention relates to a novel organic germanium compound. [Prior art] 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. For example, a compound called carboxyethylgermanium sesquioxide, which is represented by the formula (GeCH 2 CH 2 COOH) 2 O 3 , exhibits extremely strong physiological activities such as hypotensive and antitumor effects, but has no toxicity or side effects. It seems to be a well-known fact in the medical academic society that there is no such thing. [Problems to be solved by the invention] Although the mechanisms of the blood pressure lowering effect and antitumor effect exerted by carboxyethyl germanium sesquioxide have not yet been clearly elucidated, some researchers It has been proposed that its pharmacological action is derived from the germanium-oxygen bond, and therefore, the type of germanium-oxygen bond is different from that in the carboxyethyl germanium sesquioxide, which is a network-like and sheet-like compound. If it is possible to synthesize a new compound containing the above-mentioned compound, it is expected that the compound will exhibit excellent pharmacological effects comparable to those of the above-mentioned known compounds. [Means for Solving the Problems] Against the background of the above-mentioned circumstances, the present invention was made for the purpose of providing a novel and useful organic germanium compound, which has a structure having the general formula
【化】
（式中、R1、R2はメチル基、エチル基等の
低級アルキル基を、R3、R4は水素原子又はR1
と同様の低級アルキル基をそれぞれ表す〔但
し、R3及びR4が同時に水素原子である化合物
を除く〕）
で表されることを特徴とするものである。
以下に本発明を詳細に説明する。
本発明の化合物は、あたかも、二つの置換基
R1及び一つの水酸基OHを有するゲルマニウム原
子に、置換基R2、R3、R4を有するプロピオン酸
残基の結合したハイドロキシゲルミルプロピオン
酸誘導体が、当該分子内でエステル結合を形成し
た、即ち、γ−ラクトン型の化合物である。
ここで、式（）中の置換基R1、R2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
を表し、置換基R3、R4は水素原子又はR1と同様
の低級アルキル基をそれぞれ表している。但し、
本発明化合物において、置換基R3及びR4が同時
に水素原子となることはなく、従つて、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。[Formula, R 1 and R 2 are lower alkyl groups such as methyl group and ethyl group, R 3 and R 4 are hydrogen atoms or R 1
[However, compounds in which R 3 and R 4 are both hydrogen atoms are excluded]). The present invention will be explained in detail below. The compounds of the present invention are treated as if two substituents
A hydroxygermylpropionic acid derivative in which a propionic acid residue having substituents R 2 , R 3 , and R 4 is bonded to a germanium atom having R 1 and one hydroxyl group OH forms an ester bond within the molecule, That is, it is a γ-lactone type compound. Here, the substituents R 1 and R 2 in formula () represent a lower alkyl group such as a methyl group, an ethyl group, or a propyl group, and the substituents R 3 and R 4 are a hydrogen atom or a lower alkyl group similar to R 1 . Each represents a group. however,
In the compounds of the present invention, substituents R 3 and R 4 do not simultaneously become hydrogen atoms, and therefore, the organic germanium compounds of the present invention are typified by, for example, the compounds shown below.
【化】[ka]
【化】[ka]
【化】[ka]
【化】
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
に示すように、置換基R2、R3、R4を有するトリ
ハロゲノゲルミルプロピオン酸誘導体（）を、
置換基R1を含むグリニヤール試薬（）と反応
させてトリアルキルゲルミルプロピオン酸誘導体
（）とし、このトリアルキルゲルミルプロピオ
ン酸誘導体（）に例えばブロムBr2等を作用さ
せてGe−Ｒ結合を切断すると共にゲルマニウム
をブロム化してモノブロム体（）とし、該モノ
ブロム体（）を加水分解反応に付せば良いので
ある。[Chemical formula] The compound of the present invention having such a structure can be synthesized by various methods. For example, as shown in the reaction formula below, trihalogenogermylpropionic acid having substituents R 2 , R 3 , and R 4 derivative (),
A trialkylgermylpropionic acid derivative () is obtained by reacting with a Grignard reagent ( ) containing a substituent R 1 , and a Ge-R bond is formed by reacting this trialkylgermylpropionic acid derivative ( ) with, for example, bromine Br 2 . All that is required is to cleave and bromine germanium to obtain a monobromine (), and then subject the monobromine () to a hydrolysis reaction.
而して、本発明の有機ゲルマニウム化合物は、
従来公知の化合物には見られないゲルマニウム−
酸素結合を含むγ−ラクトン構造の化合物である
ので、冒頭で述べた公知化合物であるカルボキシ
エチルゲルマニウムセスキオキサイドに勝るとも
劣らない優れた薬理作用を発揮することが期待さ
れる。
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、本発明化合物は、極めて低い
濃度であつても、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。
従つて、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ず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。
〔実施例〕
１ 本発明有機ゲルマニウム化合物の合成
ａ 化合物（）の合成
３−トリクロルゲルミルプロピオン酸〈（）
に於いてR2＝R3＝R4＝Ｈ，Ｘ＝Clの化合物〉
100g（0.40mol）を無水エチルエーテルに溶解し、
氷冷下メチルマグネシウムヨーダイド〈（）に
於いてR1＝CH3の化合物〉を1.80mol含有するエ
ーテル溶液を加えた後、30分間加熱還流した。反
応終了後、希塩酸（3.5％）で加水分解し、エー
テル層を分取してから該エーテル層に無水硫酸ナ
トリウムを加えて脱水し、エーテルを留去してか
ら残渣を減圧蒸溜に付すと、化合物
（CH3）3GeCH2CH2COOH〈（）に於いてR1＝
CH3，R2＝R3＝R4＝Ｈの化合物〉の無色透明の
留分を60.9g得た。
他の化合物（）も上記と略同様の合成操作に
より得ることができたので、本発明化合物を合成
するための出発物質である化合物（）の物理化
学的データを次の表1a及びｂに示す。
Therefore, the organic germanium compound of the present invention is
Germanium, which is not found in conventionally known compounds.
Since it is a compound with a γ-lactone structure containing an oxygen bond, it is expected to exhibit pharmacological effects comparable to those of carboxyethyl germanium sesquioxide, a known compound mentioned at the beginning. In fact, the compound of the present invention is made to act on opioid-degrading enzymes that degrade 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, the compound of the present invention showed a strong inhibitory effect on specific opioid degrading enzymes even at extremely low concentrations. Therefore, the compound of the present invention can be used as an opioid-degrading enzyme inhibitor to effectively utilize administered morphine, etc. in vivo, and to reduce the dose of morphine, etc., which is highly addictive. . [Example] 1 Synthesis of the organic germanium compound of the present invention a Synthesis of compound () 3-Trichlorogermylpropionic acid ()
A compound where R 2 = R 3 = R 4 = H, X = Cl>
Dissolve 100g (0.40mol) in anhydrous ethyl ether,
After adding an ether solution containing 1.80 mol of methylmagnesium iodide (a compound where R 1 =CH 3 in ()) under ice cooling, the mixture was heated under reflux for 30 minutes. After the reaction is completed, hydrolysis is performed with dilute hydrochloric acid (3.5%), the ether layer is separated, anhydrous sodium sulfate is added to the ether layer to dehydrate it, the ether is distilled off, and the residue is subjected to vacuum distillation. Compound (CH 3 ) 3 GeCH 2 CH 2 COOH〈R 1 = in ()
60.9 g of a colorless and transparent fraction of a compound of CH 3 , R 2 =R 3 =R 4 =H was obtained. Other compounds () could also be obtained by substantially the same synthetic procedures as above, and the physicochemical data of compounds (), which are the starting materials for synthesizing the compounds of the present invention, are shown in Tables 1a and b below. .
【表】【table】
【表】
ｂ 化合物（）の合成
上記合成した（CH3）3GeCH2CH2COOH38.2g
（0.2mol）に対し、氷冷下で臭素（Br2）32.0g
（0.2mol）の四塩化炭素溶液を加えて１時間撹拌
した。反応終了後、析出する結晶をヘキサンより
再結晶すると、
Br（CH3）2GeCH2CH2COOH〈（）に於いてR1
＝CH3，R2＝R3＝R4＝Ｈの化合物〉を47.0g得
た。
他の化合物（）も上記と略同様の合成操作に
より得ることができたので、本発明化合物を合成
するための中間物質である化合物（）の物理化
学的データを次の表2a及びｂに示す。[Table] b Synthesis of compound () 38.2g of (CH 3 ) 3 GeCH 2 CH 2 COOH synthesized above
(0.2mol), 32.0g of bromine (Br 2 ) under ice cooling
(0.2 mol) of carbon tetrachloride solution was added and stirred for 1 hour. After the reaction is complete, the precipitated crystals are recrystallized from hexane, resulting in Br(CH 3 ) 2 GeCH 2 CH 2 COOH〈R 1
=CH 3 , R 2 = R 3 = R 4 = H Compound> was obtained in an amount of 47.0 g. Other compounds () could also be obtained by substantially the same synthetic procedures as above, and the physicochemical data of compounds (), which are intermediates for synthesizing the compounds of the present invention, are shown in Tables 2a and b below. .
【表】【table】
【表】
ｃ 本発明化合物（）の合成
上記合成したBr（CH3）2GeC（CH3）2CH2COOH
の5.0g（0.025モル）を20mlのクロロホルムに溶解
し、この溶液に対し20mlの水を加え、撹拌した。
反応終了後、水酸化ナトリウム水溶液により液性
が中性となるようにし、クロロホルム層を分取し
てクロロホルムを留去すると結晶が析出するの
で、これをベンゼンから再結晶すると、化合物[Table] c Synthesis of the compound of the present invention () Br(CH 3 ) 2 GeC(CH 3 ) 2 CH 2 COOH synthesized above
5.0 g (0.025 mol) of was dissolved in 20 ml of chloroform, and 20 ml of water was added to this solution and stirred.
After the reaction is complete, make the liquid neutral with an aqueous sodium hydroxide solution, separate the chloroform layer, and distill off the chloroform to precipitate crystals. When this is recrystallized from benzene, the compound
【化】
（式（）において、R1＝R2＝R3＝CH3、R4
＝Ｈの化合物）を3.03g得た。
他の化合物（）も上記と略同様の合成操作に
より得ることができたので、本発明の目的化合物
である（）の物理化学的データを次の表3a及
びｂに示す。[C] (In formula (), R 1 = R 2 = R 3 = CH 3 , R 4
3.03g of compound =H) was obtained. Since other compounds () could also be obtained by synthetic operations substantially similar to those described above, the physicochemical data of (), which is the target compound of the present invention, are shown in Tables 3a and b below.
【表】
２ 本発明有機ゲルマニウム化合物の薬理作用
現在では多種類のオピオイドペプタイド及び対
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in vitroで検
定することとした。
即ち、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、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４に
示すように本発明化合物は低濃度であつてもオピ
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、ゲルマニウムに結合する置換基
の種類によつて、猿脳由来のアミノペプチデース
或いはジペプチジルアミノペプチデースの一方を
阻害し、つまり選択性を有していることが明らか
となつたのである。[Table] 2 Pharmacological action of the organogermanium compound of the present invention At present, many types of opioid peptides and corresponding opioid peptide degrading enzymes have been discovered. I decided to test it. That is, an opioid peptide degrading enzyme was allowed to act on an opioid peptide or its model compound in the presence of the compound of the present invention, and the inhibitory effect of the compound of the present invention was measured. As a result, as shown in Table 4 below, the inhibitory effect of the compound of the present invention effectively inhibits the action of opioid peptide-degrading enzymes even at low concentrations,
Moreover, the opioid peptide degrading enzyme used this time inhibits either aminopeptidase or dipeptidyl aminopeptidase derived from monkey brain, depending on the type of substituent that binds to germanium, that is, it has selectivity. It became clear that there was.
【表】
尚、上記表４中の数値は本発明化合物を１mg／
mlの濃度で使用した場合の阻止率を％で表したも
のである。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、ACEはア
ンジオテンシン変換酵素をそれぞれ表している。
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。[Table] The values in Table 4 above are based on the amount of the compound of the present invention at 1 mg/
The inhibition rate is expressed in % when used at a concentration of ml. Also, AP is aminopeptidase, DPP
stands for dipeptidyl aminopeptidase, and ACE stands for angiotensin converting enzyme. Since the present invention is as described above, it has great industrial applicability as an organic germanium compound.
Claims (1)
低級アルキル基を、R3、R4は水素原子又はR1
と同様の低級アルキル基をそれぞれ表す〔但
し、R3及びR4が同時に水素原子である化合物
を除く〕） で表されることを特徴とする有機ゲルマニウム化
合物。[Claims] 1 General formula [Formula] (In the formula, R 1 and R 2 are lower alkyl groups such as methyl group and ethyl group, and R 3 and R 4 are hydrogen atoms or R 1
(Excluding compounds in which R 3 and R 4 are both hydrogen atoms).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59-281002 | 1984-12-29 | ||
| JP28100284 | 1984-12-29 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33503592A Division JPH0699312B2 (en) | 1984-12-29 | 1992-11-19 | Opioid-degrading enzyme inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61267591A JPS61267591A (en) | 1986-11-27 |
| JPH0583558B2 true JPH0583558B2 (en) | 1993-11-26 |
Family
ID=17632898
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27175085A Granted JPS61267591A (en) | 1984-12-29 | 1985-12-03 | Organogermanum compound |
| JP33503592A Expired - Lifetime JPH0699312B2 (en) | 1984-12-29 | 1992-11-19 | Opioid-degrading enzyme inhibitor |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33503592A Expired - Lifetime JPH0699312B2 (en) | 1984-12-29 | 1992-11-19 | Opioid-degrading enzyme inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JPS61267591A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2724397B2 (en) * | 1989-01-30 | 1998-03-09 | 株式会社浅井ゲルマニウム研究所 | Organic germanium compound and method for producing the same |
-
1985
- 1985-12-03 JP JP27175085A patent/JPS61267591A/en active Granted
-
1992
- 1992-11-19 JP JP33503592A patent/JPH0699312B2/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| CHEMICAL ABSTRACTS=1972 * |
| J.HETEROCYCL.CHEM=1974 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05238935A (en) | 1993-09-17 |
| JPS61267591A (en) | 1986-11-27 |
| JPH0699312B2 (en) | 1994-12-07 |
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