JPS5914032B2 - Bistrimethoxybenzylpiperazinoalkanes - Google Patents
BistrimethoxybenzylpiperazinoalkanesInfo
- Publication number
- JPS5914032B2 JPS5914032B2 JP51040784A JP4078476A JPS5914032B2 JP S5914032 B2 JPS5914032 B2 JP S5914032B2 JP 51040784 A JP51040784 A JP 51040784A JP 4078476 A JP4078476 A JP 4078476A JP S5914032 B2 JPS5914032 B2 JP S5914032B2
- Authority
- JP
- Japan
- Prior art keywords
- substance
- hydrochloride
- recrystallized
- yield
- hours
- 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
Links
- 239000000126 substance Substances 0.000 claims description 9
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
- SEQRDAAUNCRFIT-UHFFFAOYSA-N 1,1-dichlorobutane Chemical compound CCCC(Cl)Cl SEQRDAAUNCRFIT-UHFFFAOYSA-N 0.000 description 1
- RQXXCWHCUOJQGR-UHFFFAOYSA-N 1,1-dichlorohexane Chemical compound CCCCCC(Cl)Cl RQXXCWHCUOJQGR-UHFFFAOYSA-N 0.000 description 1
- OQYNFBPKTVQOKO-UHFFFAOYSA-N 1,1-dichlorooctane Chemical compound CCCCCCCC(Cl)Cl OQYNFBPKTVQOKO-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MIZIOHLLYXVEHJ-UHFFFAOYSA-N 2-[benzyl(2-hydroxyethyl)amino]ethanol Chemical class OCCN(CCO)CC1=CC=CC=C1 MIZIOHLLYXVEHJ-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960001177 trimetazidine Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は次の一般式 ＣＨ３ＯＯＣＨ３ １２）ｎ−〇ＣＨ２さ０ＣＨ３（Ｉ） ＊血性心疾患治療剤として有用である。[Detailed description of the invention] The present invention is based on the following general formula CH3OOCH3 12) n-○CH2sa0CH3(I) *Useful as a therapeutic agent for blood-related heart disease.
これら薬理作用の一例として、モルモツト摘出心臓にお
けるＬａｎｇｅｎｄｏｒｆｆ法による心臓脈管に対する
活性およびマウスに対するＬＤ５ｏ値を第１表ゞ０ に
示す。As an example of these pharmacological actions, Table 1 shows the activity on cardiovascular vessels according to the Langendorff method in isolated hearts of guinea pigs and the LD5o value for mice.
表
これらの化合物はいずれも種々の方法によつて合成する
ことが最も一般的には次の化学構造式（ｌ）で表わされ
るトリメタジジン２モルにジハロゲノアルカン１モルを
作用せしめる事により容易に合成する事ができる。Table All of these compounds can be synthesized by various methods, but most commonly, they can be easily synthesized by reacting 1 mole of dihalogenoalkane with 2 moles of trimetazidine, which is represented by the following chemical structure (l). I can do that.
又ジピペラジノアルカンをベンジル化する方法やＮ−ベ
ンジルジエタノールアミンの活性化誘導体２モルとジア
ミノアルカン１モルとによりピペラジン環閉環を行なう
方法等も有利に使用し得る。以下実施例により更に具体
的に説明する。Also advantageously used are a method of benzylating a dipiperazinoalkane and a method of performing piperazine ring closure using 2 moles of an activated derivative of N-benzyldiethanolamine and 1 mole of a diaminoalkane. This will be explained in more detail below with reference to Examples.
実施例 １
（ｎ＝２）
（）物質塩酸塩１０．０７、無水炭酸カリウム１３７お
よびジブロムエタン５．６ｙをＤＭＦｌＯＯｍｌ中５０
〜６０℃で３時間加温攪拌、以下常法により処理して得
られる塩基性物質をアセトンより再結晶する。Example 1 (n=2) (10.07% of the substance hydrochloride, 137% of anhydrous potassium carbonate and 5.6y of dibromoethane in 50ml of DMFlOOml)
The basic substance obtained by heating and stirring at ~60° C. for 3 hours and subsequent treatment using a conventional method is recrystallized from acetone.
融点１２１〜１２２℃、収量３．９ｔ０
実施例 ２
（ｎ＝４）
（ｌ）物質塩酸塩５．０７、無水炭酸カリウム９．０７
、ジクロルブタン１．０ＶをＤＭＳＯｌＯＯｄ中６０〜
７０℃で１０時間加温攪拌、以下常法により処理し、塩
基性物質をクロロホルム抽出。Melting point 121-122°C, yield 3.9t0 Example 2 (n=4) (l) Substance hydrochloride 5.07, anhydrous potassium carbonate 9.07
, dichlorobutane 1.0V in DMSOlOOd 60~
The mixture was heated and stirred at 70°C for 10 hours, followed by treatment using a conventional method, and basic substances were extracted with chloroform.
クロロホルム抽出液を稀塩酸と振盪し、塩酸層をアルカ
リ性として目的物質をエーテル抽出する。マレイン酸４
モルを加えてマレイン酸塩としてイソプロパノールより
再結晶する。融点９５〜９８℃、収量１．５０７。The chloroform extract is shaken with dilute hydrochloric acid, the hydrochloric acid layer is made alkaline, and the target substance is extracted with ether. maleic acid 4
The maleate salt is recrystallized from isopropanol. Melting point 95-98°C, yield 1.507.
実施例 ３
（ｎ−６）
（ｌ）物質塩酸塩６．７７、ジクロロヘキサン１．８７
および無水炭酸カリウム７．０７をＤＭＦ７Ｏｍｌ中５
０〜６０℃で１６時間加温撹拌、常法により処理し、塩
基性物質をクロロホルムで抽出後１％酢酸水で逆抽出し
、酢酸層より目的物質を得る。Example 3 (n-6) (l) Substance hydrochloride 6.77, dichlorohexane 1.87
and anhydrous potassium carbonate 7.07 in DMF 70ml
The mixture is heated and stirred at 0 to 60°C for 16 hours, treated in a conventional manner, and the basic substance is extracted with chloroform, followed by back extraction with 1% aqueous acetic acid, and the target substance is obtained from the acetic acid layer.
塩酸塩とし含水ジオキサンより再結晶する。It is converted into hydrochloride and recrystallized from aqueous dioxane.
融点２３『Ｃ（分解）、収量０．９５７０実施例 ４
（ｎ−８）
（）物質塩酸塩９．０ｙ１ジクロロオクタン３．０ｆ７
および無水炭酸カリウム１６１をＤＭＦ７Ｏｍｌ中６５
〜７０℃で１２時間加温攪拌、以下実施例３と同様に処
理し、塩酸塩とし含水イソプロパノールより再結晶する
。Melting point 23'C (decomposition), yield 0.9570 Example 4 (n-8) () Substance hydrochloride 9.0y1 dichlorooctane 3.0f7
and anhydrous potassium carbonate 161 in DMF 70ml
The mixture was heated and stirred at ~70°C for 12 hours, then treated in the same manner as in Example 3, and recrystallized from aqueous isopropanol to form a hydrochloride.
融点２３０℃以上（分解）、収量２．２７。Melting point: 230°C or higher (decomposition), yield: 2.27.
Claims (1)
は２〜８の整数を示す。 ）で表わされるビストリメトキシベンジルピペラジノア
ルカン類。[Claims] 1. The following general formula (I), that is, ▲ there are mathematical formulas, chemical formulas, tables, etc. ▼ (I) (in the formula, n
represents an integer from 2 to 8. ) bistrimethoxybenzylpiperazino alkanes represented by
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51040784A JPS5914032B2 (en) | 1976-04-09 | 1976-04-09 | Bistrimethoxybenzylpiperazinoalkanes |
| US05/783,561 US4100285A (en) | 1976-04-09 | 1977-04-01 | N-substituted trialkoxybenzyl piperazine derivatives |
| DE19772714996 DE2714996A1 (en) | 1976-04-09 | 1977-04-04 | N-SUBSTITUTED TRIALCOXYBENZYLPIPERAZINE DERIVATIVES |
| GB14537/77A GB1565431A (en) | 1976-04-09 | 1977-04-06 | N-substituted trialkoxybenzylpiperazine derivatives |
| CH446277A CH629196A5 (en) | 1976-04-09 | 1977-04-07 | Process for the preparation of N-substituted trialkoxybenzylpiperazine derivatives |
| CH446377A CH629197A5 (en) | 1976-04-09 | 1977-04-07 | Process for the preparation of N-substituted trialkoxybenzylpiperazine derivatives |
| FR7710859A FR2347359A1 (en) | 1976-04-09 | 1977-04-08 | N-SUBSTITUTED TRIALCOXYBENZYLPIPERAZINE DERIVATIVES AND THEIR PHARMACEUTICAL USES, ESPECIALLY FOR THEIR VASODILATOR ACTION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51040784A JPS5914032B2 (en) | 1976-04-09 | 1976-04-09 | Bistrimethoxybenzylpiperazinoalkanes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS52131590A JPS52131590A (en) | 1977-11-04 |
| JPS5914032B2 true JPS5914032B2 (en) | 1984-04-02 |
Family
ID=12590238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51040784A Expired JPS5914032B2 (en) | 1976-04-09 | 1976-04-09 | Bistrimethoxybenzylpiperazinoalkanes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5914032B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR81827B (en) * | 1983-03-21 | 1984-12-12 | Boehringer Ingelheim Ltd |
-
1976
- 1976-04-09 JP JP51040784A patent/JPS5914032B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS52131590A (en) | 1977-11-04 |
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