JPS6087284A - Succinimide derivative and its acid addition salt - Google Patents
Succinimide derivative and its acid addition saltInfo
- Publication number
- JPS6087284A JPS6087284A JP10007184A JP10007184A JPS6087284A JP S6087284 A JPS6087284 A JP S6087284A JP 10007184 A JP10007184 A JP 10007184A JP 10007184 A JP10007184 A JP 10007184A JP S6087284 A JPS6087284 A JP S6087284A
- Authority
- JP
- Japan
- Prior art keywords
- piperazinyl
- butyl
- formula
- pyrimidinyl
- dicarboximide
- 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
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はＮ位にピペラジニルアルキル類の置換した環状
イミド誘導体に関する。さらに詳しくいえば本発明は抗
不安作用を有し、抗不安薬として有用な一般式（１）
〔式中 Ｒ１及びＲ２は向−または相異なって水素原子
または低級アルキル基を表わすか、またはＲ１とＲ２で
単結合を表わし、Ｒａ、 Ｒ４，Ｒ５及びＲ６は同一ま
たは相異なって水素原子まとはない。また、Ｘは窒素原
子またはメチン基を、ｎは８または４の整数を＝は単結
合または二重結合を表わす。〕
で表わされる環状イミド誘導体または医薬品として許容
されるその酸付加塩に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to cyclic imide derivatives substituted with piperazinyl alkyls at the N-position. More specifically, the present invention provides a compound of the general formula (1) which has an anxiolytic effect and is useful as an anxiolytic drug [wherein R1 and R2 independently or differently represent a hydrogen atom or a lower alkyl group, or R1 and R2 represent a single bond, and Ra, R4, R5 and R6 are the same or different and do not contain a hydrogen atom. Further, X represents a nitrogen atom or a methine group, n represents an integer of 8 or 4, and = represents a single bond or a double bond. ] The present invention relates to a cyclic imide derivative represented by the above or a pharmaceutically acceptable acid addition salt thereof.
ここで、前記一般式Ｅｌ’）で表わされる化合物におい
て、低級アルキル基としては、例えば炭素原子数１〜４
個の直鎖または分校状アルキル基が挙げられ、さらに具
体的にはメチル、エチル、ｎ−プロピル、１ｓｏ−プロ
ピル、ｎ−ブチルなどを例示することができる。Here, in the compound represented by the general formula El'), the lower alkyl group has, for example, 1 to 4 carbon atoms.
Examples include linear or branched alkyl groups, and more specific examples include methyl, ethyl, n-propyl, 1so-propyl, n-butyl, and the like.
一般式（１）で表わされる化合物の医薬品として許容さ
れる酸付加塩は、この目的に一般に用いられる無機又は
有機酸、例えば塩化水素、臭化水素、硫酸、燐酸、酢酸
、酪酸、プロピオン酸、酒石酸、クエン酸、マレイン酸
、フマール酸等と一緒に形成される。Pharmaceutically acceptable acid addition salts of the compound represented by formula (1) include inorganic or organic acids commonly used for this purpose, such as hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, acetic acid, butyric acid, propionic acid, It is formed together with tartaric acid, citric acid, maleic acid, fumaric acid, etc.
本発明化合物は種々の方法により合成し得るが、例えば
以下の方法により製造される。Although the compound of the present invention can be synthesized by various methods, for example, it is produced by the following method.
一般式（１）で示される酸無水物と一般式（１）で示さ
れるアミン誘導体とを反応させることにより一般式〔Ｉ
〕の化合物を得る。本反応は、一般的に不活性有機溶媒
中で加熱することにより行われる。By reacting the acid anhydride represented by the general formula (1) with the amine derivative represented by the general formula (1), the general formula [I
) is obtained. This reaction is generally carried out by heating in an inert organic solvent.
好ましい溶媒としては、ピリジンもしくはｎ−ブチルア
ルコールなどが挙げられる。Preferred solvents include pyridine and n-butyl alcohol.
前記一般式〔ｌ〕で表わされる原料化合物のうちＲ１お
よびＲ２が結合である化合物は公知であるか、または公
知の方法に準じて合成することができる。またＲ１およ
びＲ２が水素原子または低級アルキル基である原料化合
物は公知であるか、または以下の反応式に従って（４）
〔式中、Ｒ１′及びＲ２′は同一または相異なって水素
原子または低級アルキル基を表わし、Ｒ９Ｒ’、 Ｒ’
、 Ｒ’、 Ｘ及びｎは先と同じ意味を有する。〕本発
明の具体例としては、例えば以下のような化合物を挙げ
ることができる。Among the raw material compounds represented by the general formula [1], compounds in which R1 and R2 are a bond are known or can be synthesized according to known methods. In addition, starting compounds in which R1 and R2 are a hydrogen atom or a lower alkyl group are known, or according to the following reaction formula (4) [wherein R1' and R2' are the same or different and are a hydrogen atom or a lower alkyl group] represents a group, R9R', R'
, R', X and n have the same meaning as before. ] Specific examples of the present invention include the following compounds.
■ Ｎ−（４−（４−（２−ピリミジニル）−１−ピペ
ラジニル）ブチル）−ｔ−シクロヘキセン−１，２−ジ
カルボキシイミド。(2) N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-t-cyclohexene-1,2-dicarboximide.
■ Ｎ−（８−（４−（２−ピリミジニル）−１−ピペ
ラジニル）プロピル）−ｔ−シクロヘキセン−１，２−
ジカルボキシイミド。■ N-(8-(4-(2-pyrimidinyl)-1-piperazinyl)propyl)-t-cyclohexene-1,2-
Dicarboximide.
■ Ｎ−［４−（４−（２−ピリミジニル）−１−ピペ
ラジニル）ブチル〕−４−メチルー４−シクロヘキセン
−１，２−ジカルボキシイミド。(2) N-[4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl]-4-methyl-4-cyclohexene-1,2-dicarboximide.
■ Ｎ−（８−（４−（２−ピリミジニル）−１−ピペ
ラジニル）プロピル〕−４−メチル−４（６）
一シクロヘキセンー１．２−ジカルボキシイミド。■ N-(8-(4-(2-pyrimidinyl)-1-piperazinyl)propyl]-4-methyl-4(6) monocyclohexene-1,2-dicarboximide.
■ Ｎ−（４−（４−（２−ピリジル）−１−ピペラジ
ニル）ブチル〕−４−メチルー４−シクロヘキセン−１
，２−ジカルボキシイミド。■ N-(4-(4-(2-pyridyl)-1-piperazinyl)butyl]-4-methyl-4-cyclohexene-1
,2-dicarboximide.
■ Ｎ −（４−（４−（２−ピリミジニル）−１−ピ
ペラジニル）ブチルツー４−メチルシクロヘキサン−１
，２−ジカルボキシイミド。■ N -(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl-4-methylcyclohexane-1
,2-dicarboximide.
■ Ｎ −（８−（４−（２−ピリミジニル）−１−ピ
ペラジニル）プロピル〕−４−メチルシクロヘキサン−
１，２−シカ、ルポキシイミド。■ N -(8-(4-(2-pyrimidinyl)-1-piperazinyl)propyl]-4-methylcyclohexane-
1,2-Cica, lupoximide.
■ Ｎ−（４−（４−（２−ピリジル）−１−ピペラジ
ニル）ブチルツー４−メチルシクロヘキサン−１，２−
ジカルボキシイミド。■ N-(4-(4-(2-pyridyl)-1-piperazinyl)butyl-4-methylcyclohexane-1,2-
Dicarboximide.
ＯＮ−［４−（４−（２−ピリミジニル）−１−ピペラ
ジニル）ブチル）−８，６−シメチルー４−シクロヘキ
セン−１，２−ジカルボキシイミド。ON-[4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-8,6-dimethyl-4-cyclohexene-1,2-dicarboximide.
＠ Ｎ−（４−（４−（２−ピリミジニル）−１−ピペ
ラジニル）ブチル）−８，６−ジメチＪしく６）
ｑ〉
クロヘキサン−１，２−ジカルボキシイミド。@N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-8,6-dimethy6) q> Clohexane-1,2-dicarboximide.
■ Ｎ−（４−（４−（２−ピリミジニル）−１−ピペ
ラジニル）ブチル〕−４，５−ジメチルー４−シクロヘ
キセン−１，２−ジカルボキシイミ ド。(2) N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl]-4,5-dimethyl-4-cyclohexene-1,2-dicarboximide.
ｏ Ｎ−（４−（４−（２−ピリミジニル＞−１−ピペ
ラジニル）ブチル）−４，５−ジメチルシクロヘキサン
−１，２−ジカルボキシイミド。o N-(4-(4-(2-pyrimidinyl>-1-piperazinyl)butyl)-4,5-dimethylcyclohexane-1,2-dicarboximide.
ＯＮ−（４−（４−（２−ピリミジニル）−１−ピペラ
ジニル）ブチル−１，２−ジメチルシクロヘキサン−１
，２−ジカルボキシイミド。ON-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl-1,2-dimethylcyclohexane-1
,2-dicarboximide.
［相］ Ｎ−（８−（４−（２−ピリミジニル）−１−
ピペラジニル）プロピル−１，２−’；メチルシクロヘ
キサンー１．２−ジカルボキシイミド。[Phase] N-(8-(4-(2-pyrimidinyl)-1-
piperazinyl)propyl-1,2-'; methylcyclohexane-1,2-dicarboximide.
本発明化合物の抗不安作用はラットを用いた抗コンフリ
クト試験によって実施し得る。抗コンフリクト実験はＧ
ｅ１ｌｅｒと５ｅｉｆｆｅｒ（Ｐｓｙｃｂｏｐｈａｒ
ｍａｃｏｌｏｇｉａ 、 １ 、４８２ （１９６０）
）の方法に基づき行った。The anxiolytic effect of the compounds of the present invention can be tested in an anti-conflict test using rats. Anti-conflict experiment is G
e1ler and 5eiffer (Psychbopher
Macologia, 1, 482 (1960)
).
え
レバーを押すとエサがもら会ることを学習した空腹状態
のＷｉｓｔａｒ系雄性ラット（北山）に、レバーを押す
と同時に電撃を与えるようにすると、ラットはエサは欲
しいが電撃は恐いというわらずレバーを押してエサをと
るようになる。When hungry male Wistar rats (Kitayama) have learned that pressing a lever will give them food, we give them an electric shock at the same time they press the lever. You will be able to take food by pressing the lever.
この電撃をうけながらもレバーを押してエサをとる回数
を葛藤状態軽減作用、即ち抗不安作用の指標とする。被
験薬物は腹腔内投与（ｉ、ｐ、）し、作用の最大になる
時間帯に試験を行い、対照薬として公知の抗不安薬ジア
ゼパムを用いた。The number of times the animal presses the lever and takes the food while receiving electric shock is used as an index of the conflict-reducing effect, that is, the anxiolytic effect. The test drug was administered intraperitoneally (i,p,), and the test was conducted during the time period when its effect was at its maximum.Diazepam, a known anxiolytic drug, was used as a control drug.
例えば、本発明化合物の中のＮ−（４−（４−（２−ピ
リミジニル）−１−ピペラジニル）ブチル〕−４−メチ
ルシクロヘキサン−１，２−ジカルボキシイミド塩酸塩
（化合物Ａ；実施例１の化合物） ８ ｑ／＃ｔ（ｉ、
ｐ、 ） はジアゼパムｌｑ／＆ｇ（ｉ、 ｐ、 ）
に四速する抗コンフリクト作用即ち抗不安作用を示し、
周上合物とも一般行動に殆んど影響を与えなかった。For example, among the compounds of the present invention, N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl]-4-methylcyclohexane-1,2-dicarboximide hydrochloride (Compound A; Example 1 compound) 8 q/#t(i,
p, ) is diazepam lq/&g(i, p, )
It exhibits a four-speed anti-conflict effect, that is, an anti-anxiety effect,
Shujo compound had almost no effect on general behavior.
一方、中枢抑制性副作用例えば眠気の指標とナルヘキソ
ハルビター ｔｖ （ｈｅｘｏｂａｒｂｉｔａｌ ）
麻酔増強作用をみると、ジアゼパムは１１１１／ｋｔｉ
（ｐ。On the other hand, central depressant side effects such as drowsiness and nalhexoharbital tv (hexobarbital)
Looking at the anesthetic enhancing effect, diazepam has a 1111/kti
(p.
ｏ、 ）で有意な増強作用を示すが、本発明化合物（ハ
）はｌ ００ ＩＩＩ／ｋｉｃｐ、 Ｏ，）においても
有意な影響を及ぼさなかった。これらのことより本発明
化合物（ハ）は、中枢抑制性の副作用の弱い選択的な抗
不安薬であるといえる。o, ), but the compound of the present invention (c) had no significant effect on l 00 III/kicp, O,). From these facts, it can be said that the compound (c) of the present invention is a selective anxiolytic drug with weak central depressant side effects.
前記一般式〔Ｉ〕で表わされる本発明化合物およびその
塩は、これを抗不安剤として用いるにあたり経口的また
は非経口的に投与することができる。すなわち通常用い
られる投与形態、例えば錠剤、カプセル剤、シロップ剤
、懸濁液等の型で経口的に投与することができ、あるい
はその溶液、乳剤、懸濁液等の液剤の型にしたものを注
射の型で非経口投与することができる。The compound of the present invention represented by the general formula [I] and its salt can be administered orally or parenterally when used as an anxiolytic agent. That is, it can be administered orally in commonly used dosage forms, such as tablets, capsules, syrups, suspensions, etc., or in the form of solutions, emulsions, suspensions, etc. It can be administered parenterally in the form of an injection.
坐剤の型で直腸投与することもできる。It can also be administered rectally in the form of suppositories.
また、前記の適当な投与剤型は許容される通常の担体、
賦型剤、結合剤、安定剤などに活性化合物を配合するこ
とにより製造することができる。また注射剤型で用いる
場合には許容され（９）
る緩衝剤、溶解補助剤、等張剤等を添加することもでき
る。The appropriate dosage forms also include acceptable conventional carriers,
It can be manufactured by blending the active compound with excipients, binders, stabilizers, and the like. In addition, when used in the form of an injection, acceptable buffers, solubilizing agents, isotonic agents, etc. (9) may also be added.
投与量、投与回数は症状、年令、体重、投与形態等によ
って異なるが、通常は成人に対し１日あたり約１〜８０
０Ｍｇ好ましくは５〜１００〜を１回または数回に分け
て投与することかでか、本発明はこれによって限定され
るものではない。Dose and frequency of administration vary depending on symptoms, age, body weight, administration form, etc., but are usually about 1 to 80 doses per day for adults.
0 Mg, preferably 5 to 100 Mg, may be administered once or divided into several doses, but the present invention is not limited thereby.
参考例１
２．８−ジメチル−１，８−ブタジェン１０ ｆ （０
，１２２モル）、無水マレイン酸１１．９ ＩＩ （０
，１２２モ＃）及びヘンゼン８０にｌの混合液を室温で
１０時間攪拌した。浮遊物を枦去し、ろ液を減圧上濃縮
し、収量１８．６６Ｆ（収率８６．６％）の表記化合物
を得た。融点７８−７４℃
（１０）
参考例２４
無水４，５−ジメチル−４−シクロヘキセン−１，２−
ジカルボン酸１０ｇ（０，０５５５モル）、二酸化白金
、１５０１ｓｇ及びテトラヒドロフラン１００ ｍｌの
混合液を室温で８時間水添を行なった。浮遊物を枦去し
、炉液を減圧下濃縮し、定量的に表記化合物を得た。Reference example 1 2,8-dimethyl-1,8-butadiene 10 f (0
, 122 mol), maleic anhydride 11.9 II (0
, 122 mo#) and Hensen's 80 l mixture was stirred at room temperature for 10 hours. The suspended solids were removed and the filtrate was concentrated under reduced pressure to obtain the title compound in a yield of 18.66F (yield 86.6%). Melting point 78-74°C (10) Reference example 24 Anhydrous 4,5-dimethyl-4-cyclohexene-1,2-
A mixed solution of 10 g (0,0555 mol) of dicarboxylic acid, 1501 sg of platinum dioxide, and 100 ml of tetrahydrofuran was hydrogenated at room temperature for 8 hours. The suspended solids were removed, and the filtrate solution was concentrated under reduced pressure to quantitatively obtain the title compound.
ＩＲｖ Ｆ”ｍ（ａｍ ’）：１８６Ｌ １７６０ａｘ 参考例１あるいは２と同様にして以下の化合物を得た。IRv F”m(am ’): 186L 1760ax The following compound was obtained in the same manner as in Reference Example 1 or 2.
０無水８，６−シメチルー４−シクロヘキセン−１，２
−ジカルボン酸
融点 ４８−４５°Ｃ
Ｏ無水８，６−シメチルシクロヘキサンー１．２−ジカ
ルボン酸
■Ｒ，Ｆｉ１ｍ
ｍａｘ （ＣＭ ’）：１８５５，１７９００無水ｔ、
２−ジメチｐレー４−シクロヘキセン−１，２−ジカル
ボン酸
融点 ９８−９９”Ｃ
Ｏ無水１，２−ジメチルシクロヘキサン−１，２−ジカ
ルボン酸
Ｆｉｌｍ −１
１Ｒν （ｃｌｌ ）１８４５，１８２５，１７８０ａ
ｘ
参考例８
４−クロロブチロニトリｔし８．８１１ （０，０８２
モル）、１−（２−ピリミジニル）ピペラジン８．８ｇ
（０，０８２モル）、炭酸ナトリウム６．４ｆ（０，０
６０８，モル）及びｎ−ブチルア！レコール５０ ｍｌ
の混合液を１９時間還流した。0 Anhydrous 8,6-dimethyl-4-cyclohexene-1,2
-dicarboxylic acid melting point 48-45°C O anhydrous 8,6-dimethylcyclohexane-1,2-dicarboxylic acid ■R, Fi1m max (CM'): 1855, 17900 anhydrous t,
2-dimethylcyclohexane-1,2-dicarboxylic acid Melting point 98-99"C OAnhydrous 1,2-dimethylcyclohexane-1,2-dicarboxylic acid Film -1 1Rν (cll) 1845, 1825, 1780a
x Reference Example 8 4-chlorobutyronitrit 8.811 (0,082
mol), 1-(2-pyrimidinyl)piperazine 8.8 g
(0,082 mol), sodium carbonate 6.4f (0,0
608, mol) and n-butyl a! Recole 50ml
The mixture was refluxed for 19 hours.
反応終了後、反応液を水に空け、酢酸エチルで抽出を行
なった。有機層を飽和食塩水で洗浄を行ない硫酸マグネ
シウムで乾燥後、溶媒を減圧下留去した。残渣をシリカ
ゲルを用いてクロマトで精製を行ない、収量４．６ＩＣ
収率６２．２％）の表記化合物を得た。After the reaction was completed, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by chromatography using silica gel, yielding 4.6 IC.
The title compound was obtained with a yield of 62.2%.
ｍｐ、５６−５７°Ｃ
参考例４
Ｉ−（４−アミノブチル）−４−（２−ピリル）と乾燥
エーテル２４０ ｍｌの混合液を冷却内温−５４”Ｃに
て１−（８−シアノプロピル）−４−（２−ピリミジニ
ル）ピペラジン８ｇ（８，４６ミリモル）を乾燥エーテ
ル８０ ｇ／に溶かした溶液を滴下、同温度にて１時間
３０分保温を行なった後、水２ ｍｌを滴下した。次い
で１５％ＫＯＨ水２耐を滴下し、再び水６ ｖｔｔを滴
下した。室温で８０分間攪拌後反応液をセライトで一過
、クロロホルムで洗浄を行なった。mp, 56-57°C Reference Example 4 A mixture of I-(4-aminobutyl)-4-(2-pyryl) and 240 ml of dry ether was cooled to 1-(8-cyanobutyl) at -54"C. A solution of 8 g (8.46 mmol) of (propyl)-4-(2-pyrimidinyl)piperazine dissolved in 80 g of dry ether was added dropwise, kept at the same temperature for 1 hour and 30 minutes, and then 2 ml of water was added dropwise. Next, 2 ml of 15% KOH water was added dropwise, and then 6 ml of water was added dropwise again.After stirring at room temperature for 80 minutes, the reaction solution was passed through Celite and washed with chloroform.
炉液を減圧下濃縮を行ない、残渣をシリカゲルを用いて
クロマト精製を行ない表記化合物を得た。The furnace liquid was concentrated under reduced pressure, and the residue was purified by chromatography using silica gel to obtain the title compound.
ＩＲｖ ””ｍ（ａｓ ’）：８１００〜８６００゜ｍ
ａｘ
１５８０、．１５４０
実施例１
Ｎ−［４−（４−（２−ピリミジニル）−（１３）
１−ピペラジニル）ブチル〕−４−メチルシ無水４−メ
チＩレジクロヘキサン１，２−ジカルボン酸ｌ、７０
ｆ （１０，０ミリモル）、１−（４−アミノブチル）
−４−（２−ピリミジニル）ピペラジン２．００ｇ（８
，５０ミリモル）及び乾燥ピリジン２０ｍ１の混合液を
１２時間還流した。IRv ””m (as '): 8100~8600゜m
ax 1580,. 1540 Example 1 N-[4-(4-(2-pyrimidinyl)-(13) 1-piperazinyl)butyl]-4-methylcyanhydride 4-methyI diclohexane 1,2-dicarboxylic acid l, 70
f (10,0 mmol), 1-(4-aminobutyl)
-4-(2-pyrimidinyl)piperazine 2.00 g (8
, 50 mmol) and 20 ml of dry pyridine was refluxed for 12 hours.
次いで反応溶媒を減圧留去し、残渣を溶出液にクロロホ
ルム：メチルアルコール：アンモニア水（５００：２５
：２）を用いシリカゲルのカラムクロマトグラフィーに
よって精製した。得られた油状物を８％塩化水素／イソ
プロピルアルコールで処理し塩酸塩にした。Next, the reaction solvent was distilled off under reduced pressure, and the residue was mixed with chloroform:methyl alcohol:ammonia water (500:25) as an eluent.
:2) was purified by column chromatography on silica gel. The resulting oil was treated with 8% hydrogen chloride/isopropyl alcohol to give the hydrochloride.
イソプロピルアルコールで再結晶を行い、表記化合物を
得た。Recrystallization was performed with isopropyl alcohol to obtain the title compound.
融点 １５６−１５８°Ｃ 実施例２ 適当な出発原料を用い、実施例１と同様の（１４） 操作を行い下記化合物を合成した。Melting point: 156-158°C Example 2 (14) as in Example 1 using appropriate starting materials. The following compound was synthesized by performing the operation.
Ｎ−［：４ − （４−（２−ビリミジニ Ｊし ）−
１＝ピペラジニル）ブチル〕−１−シクロヘキセン−１
，２−’３カルボキシイミド塩酸塩
融点 １９４−１９６°Ｃ
Ｎ−［４−（４−（２−ピリミジニル）−１−ピペラジ
ニル）ブチル〕−４−メチルー４−シクロヘキセン−１
，２−ジカルボキシイミド塩酸塩
融点 １６４−１６５．５”Ｃ
Ｎ−（４−（４−（２−ピリジル）−１−ピペラジニル
）ブチル〕−４−メチルー４＝シクロヘキセン−１，２
−ジカルボキシイミド塩酸塩
融点 １２２°Ｃ（分解）
Ｎ−１１４−（４−（２−ピリジル）−１−ピペラジニ
ル）ブチＩし〕−４−メチルシクロヘキサン−１，２−
ジカルボキシイミド塩酸塩
（１５）
融点 １２５°Ｃ（分解）
Ｎ−（４−（４−（２−ピリミジニル）−１−ピペラジ
ニル）ブチル）−８，６−シメチルシクロヘキサンー１
，２−ジカルボキシイミド塩酸塩
融点 １８７°Ｃ（分解）
Ｎ−（４−（４−（２−ピリミジニル）＝■−ピペラジ
ニル）ブチＣし）−４，５−ジメチル−４−シクロヘキ
セン−１゜２−ジカルボキシイミド塩酸塩
融点 ２０９下２Ｌｌ”０
Ｎ−（４−（４−（２−ピリミジニル）−１−ピペラジ
ニル）ブチル）４．５−ジメチルシクロヘキサン−１，
２−ジカルボキシイミド塩酸塩
融点 ２２５−２２７°Ｃ
Ｎ−（４−（４−（２−ビ社ミジニル）−１−ピペラジ
ニル）ブチル：）−１，２−ジメチルシクロヘキサン−
１，２−ジカルボキシイミド塩酸塩
融点 ２０８−２１０°Ｃ（分解）
（１６完）
第１頁の続きN-[:4-(4-(2-virimijini Jshi)-
1=piperazinyl)butyl]-1-cyclohexene-1
,2-'3carboximide hydrochloride Melting point 194-196°C N-[4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl]-4-methyl-4-cyclohexene-1
,2-dicarboximide hydrochloride Melting point 164-165.5"C N-(4-(4-(2-pyridyl)-1-piperazinyl)butyl]-4-methyl-4=cyclohexene-1,2
-dicarboximide hydrochloride Melting point 122°C (decomposition) N-114-(4-(2-pyridyl)-1-piperazinyl)buty]-4-methylcyclohexane-1,2-
Dicarboximide hydrochloride (15) Melting point 125°C (decomposition) N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-8,6-dimethylcyclohexane-1
,2-dicarboximide hydrochloride Melting point 187°C (decomposition) 2-dicarboximide hydrochloride Melting point 209 below 2Ll”0 N-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)4.5-dimethylcyclohexane-1,
2-Dicarboximide hydrochloride Melting point 225-227°C N-(4-(4-(2-bi-midinyl)-1-piperazinyl)butyl:)-1,2-dimethylcyclohexane-
1,2-dicarboximide hydrochloride Melting point 208-210°C (decomposed) (16 completed) Continued from page 1
Claims (1)
子または低級アルキル基を表わすか、またはＲ１とＲ２
で単結合を表わし、Ｒ，Ｒ，Ｒ及びＲは同一まｔこは相
異なって 水素原子または低級アルキル基を表わすが、
Ｒ、Ｒ、Ｒ。 Ｒ４、Ｒ６及びＲ６が同時に水素原子を表わすことはな
い。また、Ｘは窒素原子またはメチン基を、ｎは８また
は４の整数を＝は単結合または二重結合を表わす。〕 で表わされる環状イミド誘導体または医薬品として許容
されるその酸付加塩。[Claims] General formula [wherein R1 and R2 are the same or different and represent a hydrogen atom or a lower alkyl group, or R1 and R2
represents a single bond, and R, R, R and R are the same but different and represent a hydrogen atom or a lower alkyl group,
R, R, R. R4, R6 and R6 do not represent a hydrogen atom at the same time. Further, X represents a nitrogen atom or a methine group, n represents an integer of 8 or 4, and = represents a single bond or a double bond. ] A cyclic imide derivative represented by or a pharmaceutically acceptable acid addition salt thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/543,496 US4598078A (en) | 1982-10-21 | 1983-10-19 | N-(substituted piperazinyl) alkylbicyclic succinimide derivatives |
| US543496 | 1990-06-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6087284A true JPS6087284A (en) | 1985-05-16 |
| JPH0475B2 JPH0475B2 (en) | 1992-01-06 |
Family
ID=24168308
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10007184A Granted JPS6087284A (en) | 1983-10-19 | 1984-05-17 | Succinimide derivative and its acid addition salt |
| JP11756984A Pending JPS6087262A (en) | 1983-10-19 | 1984-06-07 | Production of succinimide derivative |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11756984A Pending JPS6087262A (en) | 1983-10-19 | 1984-06-07 | Production of succinimide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JPS6087284A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0196096A2 (en) | 1985-03-27 | 1986-10-01 | Sumitomo Pharmaceuticals Company, Limited | Imide derivatives, their production and use |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4732983A (en) * | 1987-04-03 | 1988-03-22 | American Home Products Corporation | Pyschotropic polycyclic imides |
| US4797488A (en) * | 1987-04-03 | 1989-01-10 | American Home Products Corporation | Psychotropic polycyclic imides |
| US4748240A (en) * | 1987-04-03 | 1988-05-31 | American Home Products Corporation | Psychotropic bicyclic imides |
| AU2003278403A1 (en) * | 2003-10-15 | 2005-05-05 | Ranbaxy Laboratories Limited | 1-alkylpiperazinyl-pyrrolidin-2, 5-dione derivatives as adrenergic receptor antagonist |
-
1984
- 1984-05-17 JP JP10007184A patent/JPS6087284A/en active Granted
- 1984-06-07 JP JP11756984A patent/JPS6087262A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0196096A2 (en) | 1985-03-27 | 1986-10-01 | Sumitomo Pharmaceuticals Company, Limited | Imide derivatives, their production and use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0475B2 (en) | 1992-01-06 |
| JPS6087262A (en) | 1985-05-16 |
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