JPH0353301B2 - - Google Patents
Info
- Publication number
- JPH0353301B2 JPH0353301B2 JP59024074A JP2407484A JPH0353301B2 JP H0353301 B2 JPH0353301 B2 JP H0353301B2 JP 59024074 A JP59024074 A JP 59024074A JP 2407484 A JP2407484 A JP 2407484A JP H0353301 B2 JPH0353301 B2 JP H0353301B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- ethanol
- acid
- solvent
- methoxyphenyl
- 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 - Lifetime
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Description
【発明の詳細な説明】
本発明は一般式（）で示される新規なフエニ
ルピペラジン誘導体およびその塩に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel phenylpiperazine derivative represented by the general formula () and a salt thereof.
（式中Ｒは水素原子または水酸基を意味する）
一般式（）で示される化合物は新規化合物で
あり例えば以下示する方法によつて製造される。 (In the formula, R means a hydrogen atom or a hydroxyl group) The compound represented by the general formula () is a new compound and can be produced, for example, by the method shown below.
化合物（）を還元すると化合物（ａ）また
は（ｂ）が生成する。化合物（ａ）が生成す
るかまたは（ｂ）が生成するかは還元条件によ
つて異なり、例えば化合物（）の水素化ホウ素
ナトリウム還元では化合物（ａ）が得られ、亜
鉛末を用いた還元では化合物（ｂ）が得られ
る。水素化ホウ素ナトリウムによる還元は常法に
より、例えばエタノール、メタノール等のアルコ
ール中室温で数時間攪拌することにより行なわ
れ、亜鉛末を用いる還元では、化合物（）を加
温下、酢酸中１〜２時か攪拌せしめることにより
行なわれる。反応混合物から化合物（ａ）また
は（ｂ）の単離は常法により、例えば不溶物を
去した後、抽出し、水洗し、乾燥後濃縮しカラ
ムクロマトグラフイー等の手段に付すことにより
行なわれる。 Compound (a) or (b) is produced when compound () is reduced. Whether compound (a) or (b) is produced depends on the reduction conditions; for example, reduction of compound () with sodium borohydride yields compound (a), whereas reduction with zinc dust yields compound (a). Compound (b) is obtained. Reduction with sodium borohydride is carried out by a conventional method, for example, by stirring in an alcohol such as ethanol or methanol at room temperature for several hours, and reduction with zinc powder is carried out by stirring the compound () in acetic acid for 1 to 2 hours under heating. This is done by stirring for a while. Isolation of compound (a) or (b) from the reaction mixture is carried out by a conventional method, for example, by removing insoluble materials, extracting, washing with water, drying, concentrating, and subjecting to means such as column chromatography. .
本発明の化合物（ａ）または（ｂ）は種々
の有機酸または無機酸と塩を形成する。塩として
は薬学的に許容される酸の塩が好ましく、このよ
うな酸としては例えば、塩酸、硫酸、硝酸、リン
酸等の無機酸およびフマール酸、マレイン酸、酒
石酸、コハク酸等の有機酸がある。塩は常法に従
い容易に製造することができる。 Compounds (a) or (b) of the invention form salts with various organic or inorganic acids. The salt is preferably a salt of a pharmaceutically acceptable acid, and examples of such acids include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid, and organic acids such as fumaric acid, maleic acid, tartaric acid, and succinic acid. There is. Salts can be easily produced according to conventional methods.
このようにして製造した本発明の化合物は降圧
作用、脳血流増大作用および心拍数を減少せし
め、かつ心筋虚血による心室性不整脈を抑制する
作用を有し降圧剤、抗不整脈剤、虚血性心疾患治
療剤および末梢血管拡張剤等の循環器疾患治療剤
として有用である。 The compound of the present invention thus produced has antihypertensive effects, cerebral blood flow increasing effects, decreases heart rate, and suppresses ventricular arrhythmia caused by myocardial ischemia. It is useful as a therapeutic agent for cardiovascular diseases such as a therapeutic agent for heart diseases and a peripheral vasodilator.
参考例
Ｎ−（２−ブロモエチル）フタルイミド10.08
ｇ、１−（２−メトキシフエニル）ピペラジン
7.68ｇ、トリエチルアミン10mlをトルエン100ml
中攪拌下３時間還流する。反応後水を加え、トル
エンで抽出する。抽出液を水洗、芒硝で乾燥後濃
縮し、シリカゲルを用いたカラムクロマトグラフ
イー（溶媒クロロホルム）に付すと5.70ｇのＮ−
２−〔４−（２−メトキシフエニル）−１−ピペラ
ジニル〕エチルフタルイミドを赤褐色の油状物と
して得る。Reference example N-(2-bromoethyl)phthalimide 10.08
g, 1-(2-methoxyphenyl)piperazine
7.68g, triethylamine 10ml to toluene 100ml
Reflux for 3 hours under medium stirring. After the reaction, water is added and extracted with toluene. The extract was washed with water, dried with Glauber's salt, concentrated, and subjected to column chromatography using silica gel (solvent: chloroform) to yield 5.70 g of N-
2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylphthalimide is obtained as a reddish-brown oil.
実施例 １
参考例で得たＮ−２−〔４−（２−メトキシフエ
ニル）−１−ピペラジニル〕エチルフタルイミド
2.88ｇを150mlのメタノールに溶解し、これに水
酸化ホウ素ナトリウム800mgを加え室温で５時間
攪拌する。減少下溶媒を留去して得られる残渣よ
りジクロルメタンで抽出し、飽和食塩水で洗浄し
無水硫酸ナトリウムで乾燥後減圧溶媒を留去して
得られる油状物をシリカゲルカラムクロマトグラ
フイー（溶媒クロロホルム：エタノール＝50：
１）に付し無色粉末の２−〔２−〔４−（２−メト
キシフエニル）−１−ピペラジニル〕エチル〕−３
−ハイドロキシフタリミジンを得る。IRスペク
トル（KBr）：3360，1695cm-1。これをエタノー
ルに溶解し塩化水素ガスを飽和し塩酸塩となしエ
タノールを留去後得られる粗結晶をエタノール−
ｎ−ヘキサンより再結晶すると融点149〜156℃
（分解）の無色針状晶2.30ｇを得る。Example 1 N-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl phthalimide obtained in Reference Example
Dissolve 2.88 g in 150 ml of methanol, add 800 mg of sodium borohydroxide, and stir at room temperature for 5 hours. The residue obtained by distilling off the solvent under reduced pressure was extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.The resulting oil was subjected to silica gel column chromatography (solvent: chloroform: Ethanol = 50:
1) to obtain a colorless powder of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-3.
- Obtain hydroxyphthalimidine. IR spectrum (KBr): 3360, 1695cm -1 . This is dissolved in ethanol, saturated with hydrogen chloride gas to form a hydrochloride salt, and the crude crystals obtained after distilling off the ethanol are ethanol-
Melting point: 149-156℃ when recrystallized from n-hexane
(Decomposition) 2.30 g of colorless needle crystals are obtained.
実施例 ２
参考例で得たＮ−２−〔４−（２−メトキシフエ
ニル）−１−ピペラジニル〕エチルフタルイミド
2.00ｇ、亜鉛末200ｇ、酢酸50mlの混合物を65〜
70℃で１時間攪拌する。付溶物を別後減圧下溶
媒を留去し得られる残渣をジクロルメタンで抽出
する。抽出液を飽和炭酸水素ナトリウム水次いで
飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥
後減圧下溶媒を留去して得られる油状物をシルカ
ゲルカラムクロマトグラフイー（溶媒クロロホル
ム：エタノール＝500：６）に付し無色油状物の
Ｎ−２−〔４−（２−メトキシフエニル）−１−ピ
ペラジニル〕エチルフタリミジンを得る。これを
エタノールに溶解し塩化水素を飽和し塩酸塩とな
しエタノールを留去して得られる粗結晶をエタノ
ール−ｎ−ヘキサンより再結晶して分解開始点
160℃の無色針状晶1.67ｇを得る。IRスペクトル
（KBr）：2450〜2220，1710cm-1。Example 2 N-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl phthalimide obtained in Reference Example
A mixture of 2.00g, 200g of zinc powder, and 50ml of acetic acid for 65~
Stir at 70°C for 1 hour. After separating the solute, the solvent is distilled off under reduced pressure and the resulting residue is extracted with dichloromethane. The extract was washed with saturated sodium bicarbonate water and then saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting oil was subjected to silica gel column chromatography (solvent chloroform:ethanol = 500:6). ) to obtain N-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylphthalimidine as a colorless oil. This is dissolved in ethanol, saturated with hydrogen chloride to form a hydrochloride salt, and the crude crystals obtained by distilling off the ethanol are recrystallized from ethanol-n-hexane to reach the starting point of decomposition.
1.67 g of colorless needles at 160° C. are obtained. IR spectrum (KBr): 2450-2220, 1710cm -1 .
Claims (1)
示されるフエニルピペラジン類およびその塩。[Claims] 1. General formula (In the formula, R means a hydrogen atom or a hydroxyl group.) Phenylpiperazines and salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59024074A JPS60169461A (en) | 1984-02-10 | 1984-02-10 | 2-methoxyphenylpiperazine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59024074A JPS60169461A (en) | 1984-02-10 | 1984-02-10 | 2-methoxyphenylpiperazine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60169461A JPS60169461A (en) | 1985-09-02 |
| JPH0353301B2 true JPH0353301B2 (en) | 1991-08-14 |
Family
ID=12128273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59024074A Granted JPS60169461A (en) | 1984-02-10 | 1984-02-10 | 2-methoxyphenylpiperazine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60169461A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0168003B1 (en) * | 1984-07-06 | 1991-04-03 | Otsuka Pharmaceutical Co., Ltd. | Oxindol compounds, compositions containing same and processes for preparing same |
| FR2628425B1 (en) * | 1988-03-08 | 1992-04-03 | Rhone Poulenc Sante | ISOINDOLINONE DERIVATIVES, THEIR PREPARATION METHODS AND THE MEDICINAL PRODUCTS CONTAINING THEM |
-
1984
- 1984-02-10 JP JP59024074A patent/JPS60169461A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60169461A (en) | 1985-09-02 |
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