JPH0140032B2 - - Google Patents
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- JPH0140032B2 JPH0140032B2 JP54171617A JP17161779A JPH0140032B2 JP H0140032 B2 JPH0140032 B2 JP H0140032B2 JP 54171617 A JP54171617 A JP 54171617A JP 17161779 A JP17161779 A JP 17161779A JP H0140032 B2 JPH0140032 B2 JP H0140032B2
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- Prior art keywords
- formula
- compound
- acid
- present
- group
- 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.)
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- Thiazole And Isothizaole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は式〔〕で示される化合物およびその
塩類に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a compound represented by the formula [] and salts thereof.
〔式中、R1はヒドロキシ基または低級アルカ
ノイルオキシ基を示し、R2は水素原子またはベ
ンゾイル基を示す。Ｑは１〜３個の炭素原子を有
する直鎖または分枝のアルキレンを示し、ｎは２
を示す。以下同じ。〕低級アルカノイルオキシ基
としてはアセトキシ、プロパノイルオキシまたは
ブタノイルオキシをあげることができる。 [In the formula, R 1 represents a hydroxy group or a lower alkanoyloxy group, and R 2 represents a hydrogen atom or a benzoyl group. Q represents straight-chain or branched alkylene having 1 to 3 carbon atoms, n is 2
shows. same as below. ] Examples of the lower alkanoyloxy group include acetoxy, propanoyloxy and butanoyloxy.
本発明化合物は特開昭54−148783号および特願
昭54−84827号（特開昭56−8317号公報参照）に
開示した化合物と構造式の基本骨格が類似し、ア
ンジオテンシン変換酵素およびアルドース還元酵
素を阻害することから血圧降下剤および糖尿病合
併症の予防ならびに治療剤として有用なものであ
る。 The compound of the present invention has a basic structural formula similar to the compounds disclosed in JP-A-54-148783 and JP-A-54-84827 (see JP-A-56-8317), and has angiotensin converting enzyme and aldose reducing enzyme. Since it inhibits enzymes, it is useful as a hypotensive agent and as a preventive and therapeutic agent for diabetic complications.
本発明化合物は例えば次のＡおよびＢのような
方法で合成される。 The compound of the present invention can be synthesized, for example, by the following methods A and B.
Ａ 式〔〕
R3−Ｓ−Ｑ−COOH 〔〕
〔式中、R3は前記R2に示される基または
HOOC−Ｑ−Ｓ−を示す。以下同じ。〕で表わさ
れる化合物を反応性誘導体（例えば酸ハライド、
酸無水物、混合酸無水物、活性エステル等）に導
き、それと式〔〕
で表わされる化合物を一般的方法により反応させ
ると、式〔〕
〔式中、R4は前記R2に示される群より水素原
子を除いた基を示す。〕で表わされる本発明化合
物を得る。次いで、この生成物〔〕を塩酸、パ
ラトルエンスルホン酸等の酸処理、水酸化ナトリ
ウム、アンモニア等のアルカリ処理、必要な場合
は白金触媒による接触還元、電解還元、水素化ホ
ウ素ナトリウム等の金属水素錯化合物による還元
または金属による還元等の方法により、式〔〕
においてR2が水素原子である本発明化合物を得
ることができる。A Formula [] R 3 -S-Q-COOH [] [In the formula, R 3 is the group shown in R 2 above or
HOOC-Q-S- is shown. same as below. ] to reactive derivatives (e.g. acid halides,
acid anhydrides, mixed acid anhydrides, active esters, etc.), and the formula [] When the compound represented by is reacted by a general method, the formula [] [In the formula, R 4 represents a group obtained by removing a hydrogen atom from the group shown in R 2 above. The compound of the present invention represented by the following formula is obtained. Next, this product [] is treated with an acid such as hydrochloric acid or para-toluenesulfonic acid, an alkali treatment such as sodium hydroxide or ammonia, and if necessary, catalytic reduction using a platinum catalyst, electrolytic reduction, or metal hydrogen treatment such as sodium borohydride. By methods such as reduction with a complex compound or reduction with a metal, the formula []
A compound of the present invention in which R 2 is a hydrogen atom can be obtained.
Ｂ 式〔〕
Ｙ−Ｑ−COOH 〔〕
〔式中、Ｙはハロゲン原子を示す。〕で表わさ
れる化合物と前記化合物〔〕を前記Ａの方法に
従つて反応させると式〔〕
で表わされる化合物を得る。次いで、この化合物
〔〕とチオ安息香酸または二硫化ナトリウム等
の含硫化合物を反応させると本発明化合物を得る
ことができる。B Formula [] Y-Q-COOH [] [In the formula, Y represents a halogen atom. ] When the compound represented by [] is reacted with the compound [] according to method A above, the formula [] A compound represented by is obtained. Next, the compound of the present invention can be obtained by reacting this compound [] with a sulfur-containing compound such as thiobenzoic acid or sodium disulfide.
上記の方法により合成した式〔〕で示される
本発明化合物は必要に応じてナトリウム、カリウ
ム、カルシウム、マグネシウム、アルミニウム、
アンモニウム、ジエチルアミン、Ｎ−メチルグル
カミンまたはトリエタノールアミン等の医薬とし
て許容される塩とすることができる。 The compound of the present invention represented by the formula [] synthesized by the above method may contain sodium, potassium, calcium, magnesium, aluminum,
It can be a pharmaceutically acceptable salt such as ammonium, diethylamine, N-methylglucamine or triethanolamine.
なお、本発明化合物は１個またはそれ以上の不
整炭素を有する故、立体異性体が存在する。これ
らはいずれも本発明の範囲に包含されるものであ
る。以下に実施例を示すが本発明はそれらに限定
されない。 In addition, since the compound of the present invention has one or more asymmetric carbon atoms, stereoisomers exist. All of these are included within the scope of the present invention. Examples are shown below, but the present invention is not limited thereto.
実施例 １
（4R）−２−（２−アセトキシシクロヘキシル）
−３−（Ｓ−ベンゾイル−３−メルカプトプロ
パノイル）−４−チアゾリジンカルボン酸の製
造
（4R）−２−（２−アセトキシシクロヘキシル）
−４−チアゾリジンカルボン酸（融点143−145℃
（分解））8.2ｇ（0.03モル）およびトリエチルア
ミン6.1ｇ（0.06モル）を無水アセトン150mlに溶
解し、氷冷下攪拌しながらＳ−ベンゾイル−３−
メルカプトプロパノイルクロリド6.9ｇ（0.03モ
ル）を滴下する。滴下終了後、氷冷下１時間、さ
らに室温で１時間攪拌する。酢酸1.7ml（0.03モ
ル）を加え、沈殿物を取する。液を減圧濃縮
し、得られた油状物を酢酸エチル80mlに溶解す
る。有機層を水、飽和食塩水で洗浄し、硫酸マグ
ネシウムで脱水後、減圧濃縮して油状物14.2ｇを
得る。この油状物をシリカゲルカラムクロマトに
より精製して標記化合物12.0ｇ（収率86％）を得
る。Example 1 (4R)-2-(2-acetoxycyclohexyl)
Production of -3-(S-benzoyl-3-mercaptopropanoyl)-4-thiazolidinecarboxylic acid (4R)-2-(2-acetoxycyclohexyl)
-4-thiazolidinecarboxylic acid (melting point 143-145℃
(Decomposition)) 8.2 g (0.03 mol) and 6.1 g (0.06 mol) of triethylamine were dissolved in 150 ml of anhydrous acetone, and while stirring under ice cooling, S-benzoyl-3-
6.9 g (0.03 mol) of mercaptopropanoyl chloride is added dropwise. After completion of the dropwise addition, the mixture was stirred for 1 hour under ice-cooling and further stirred at room temperature for 1 hour. Add 1.7 ml (0.03 mol) of acetic acid and collect the precipitate. Concentrate the liquid under reduced pressure and dissolve the resulting oil in 80 ml of ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 14.2 g of an oil. This oily substance is purified by silica gel column chromatography to obtain 12.0 g (yield: 86%) of the title compound.
融点58−61℃
〔α〕25 D−45.7゜（ｃ＝1.2、メタノール）
IR（nujol，cm-1）1737，1650，1615，1408，
1235，1207，912
実施例 ２
（4R）−２−（２−ヒドロキシシクロヘキシル）
−３−（３−メルカプトプロパノイル）−４−チ
アゾリジンカルボン酸の製造
（4R）−２−（２−アセトキシシクロヘキシル）
−３−（Ｓ−ベンゾイル−３−メルカプトプロパ
ノイル）−４−チアゾリジンカルボン酸4.7ｇ
（0.01モル）をメタノール50mlに溶解し、濃アン
モニア水60mlを加え、室温で1.5時間攪拌する。
アンモニアおよびメタノールを減圧留去後、酢酸
エチルで洗浄する。水層を濃塩酸で酸性にし、酢
酸エチルで抽出する。有機層を飽和食塩水で洗浄
し、硫酸マグネシウムで脱水後、減圧濃縮する。
得られた油状物をシリカゲルカラムクロマトによ
り精製して標記化合物2.7ｇ（収率84％）を得る。 Melting point 58-61℃ [α] 25 D −45.7゜ (c=1.2, methanol) IR (nujol, cm -1 ) 1737, 1650, 1615, 1408,
1235, 1207, 912 Example 2 (4R)-2-(2-hydroxycyclohexyl)
-Production of 3-(3-mercaptopropanoyl)-4-thiazolidinecarboxylic acid (4R)-2-(2-acetoxycyclohexyl)
-3-(S-benzoyl-3-mercaptopropanoyl)-4-thiazolidinecarboxylic acid 4.7g
(0.01 mol) was dissolved in 50 ml of methanol, 60 ml of concentrated aqueous ammonia was added, and the mixture was stirred at room temperature for 1.5 hours.
After distilling off ammonia and methanol under reduced pressure, the mixture is washed with ethyl acetate. The aqueous layer is made acidic with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
The obtained oil is purified by silica gel column chromatography to obtain 2.7 g (yield: 84%) of the title compound.
融点33−34℃
〔α〕25 D−32.7゜（ｃ＝1.0、メタノール）
IR（nujol，cm-1）3250，1726，1645，1408，
1045。 Melting point 33-34℃ [α] 25 D −32.7゜ (c=1.0, methanol) IR (nujol, cm -1 ) 3250, 1726, 1645, 1408,
1045.
Claims (1)
ノイルオキシ基を示し、R2は水素原子またはベ
ンゾイル基を示す。Ｑは１〜３個の炭素原子を有
する直鎖または分枝のアルキレンを示し、ｎは２
を示す。〕[Claims] 1. A compound represented by the formula [] and salts thereof. [In the formula, R 1 represents a hydroxy group or a lower alkanoyloxy group, and R 2 represents a hydrogen atom or a benzoyl group. Q represents straight-chain or branched alkylene having 1 to 3 carbon atoms, n is 2
shows. ]
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17161779A JPS5695179A (en) | 1979-12-28 | 1979-12-28 | Thiazolidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17161779A JPS5695179A (en) | 1979-12-28 | 1979-12-28 | Thiazolidine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5695179A JPS5695179A (en) | 1981-08-01 |
| JPH0140032B2 true JPH0140032B2 (en) | 1989-08-24 |
Family
ID=15926485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17161779A Granted JPS5695179A (en) | 1979-12-28 | 1979-12-28 | Thiazolidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5695179A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6141512A (en) * | 1984-08-03 | 1986-02-27 | Ikeda Bussan Co Ltd | Manufacture of head rest with holes |
-
1979
- 1979-12-28 JP JP17161779A patent/JPS5695179A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5695179A (en) | 1981-08-01 |
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