申请人:ONO PHARMACEUTICAL CO., LTD.
公开号:EP0312906A2
公开(公告)日:1989-04-26
A sulfonamide derivative of the general formula:
wherein, R1 represents
or
wherein
R11 represents a hydrogen atom, alkyl group of from 1 to 20 carbon atom(s), carbocyclic ring unsubstituted or substituted by an alkyl or alkoxy group of from 1 to 4 carbon atom(s) or halogen atom, or steroid,
R12 represents a hydrogen atom or COR'S,
R13 and R14 each represent a hydrogen atom or alkyl group of form 1 to 4 carbon atom(s) or NR13R14 represents an amino acid residue or heterocyclic ring, or
R15 represetns an alkyl group of from 1 to 4 carbon atom(s) or phenyl group,
represents
or
wherein
represents
Ba represents
or
wherein m represetns an integer of from 1 to 6, and the configuration of a double bond is E, Z or EZ and a phenylene group represetns and o-, m- or p-phenylene group in the formula (Ba-5), R2a represents a bond or an alkylene group of from 1 to 4 carbon atom(s), R3a represents a carbocyclic or heterocyclic ring unsubstituted or substituted by from one to three of an alkyl group of from 1 to 4 carbon atom(s), alkoxy group of from 1 to 4 carbon atom(s), hydroxy group, carboxyl group, ciano group, halogen atom or nitro group, or R2a represents an alkyl group of from 1 to 12 carbon atom(s) together with R3a,
represents
or
Xb represents
(i) bond,
(ii) alkylene group of from to to 4 carbon atoms or
(iii) alkenylene group of from 2 to 4 carbon atoms (with the proviso that α-CH=CHCH2β and αCH2CH=CHCH2β are exluded),
R2b represents 3
(i) hydrogen atom,
(ii) halogen atom or
(iii) alkyl group of from 1 to 4 carbon atom(s),
the configuration of a double bond between Cs and Cs in the general formula (B) is cis,
represents
or
Lc represents an alkylene group of from 1 to 4 carbon atom(s). R2c represents a hydrogen atom, alkyl group of from 1 to 4 carbon atom(s) or halogen atom,
the configuration of a double bond between Cs and Cs in the general formula (c) is cis or trans, with the proviso that when
represents the general formula (A), R" doesn't reprsents a hydrogen atom or alkyl group of from 1 to 20 carbon atom(s);
cyclodextrin clathrates thereof, or non-toxic salts thereof in case that R11 represents a hydrogen atom or NR13R14 represents an amino acid residue, possess an antagonistic activity on TXA2, in particular, inhibit blood platelet aggregation and contraction of artery, and are, therefore, useful for prevention and/or treatment of inflammation, hypertension, thrombus, cerebral apoplexy, asthma, cardiac infarction, angina pectoris, cerebral infarction and death by aucte cardiac diseases in mammales, in particular in humans, which are induced by thromboxane A2.
通式如下的磺酰胺衍生物
其中,R1 代表
或
其中
R11 代表氢原子、1 至 20 个碳原子的烷基、未被或被 1 至 4 个碳原子的烷基或 烷氧基或卤素原子取代的碳环或甾族化合物、
R12 代表氢原子或 COR'S、
R13 和 R14 分别代表氢原子或 1 至 4 个碳原子的烷基,或 NR13R14 代表氨基酸残基或杂环,或
R15 代表 1 至 4 个碳原子的烷基或苯基、
代表
或
其中
代表
Ba 代表
或
其中 m 代表 1 至 6 的整数,双键的构型为 E、Z 或 EZ,苯基代表式 (Ba-5)中的邻苯基、间苯基或对苯基,R2a 代表键或 1 至 4 个碳原子的亚烷基、R3a 代表未被取代或被 1 至 3 个碳原子的烷基、1 至 4 个碳原子的烷氧基、羟基、羧基、氰基、卤素原子或硝基取代的碳环或杂环,或 R2a 与 R3a 一起代表 1 至 12 个碳原子的烷基、
代表
或
Xb 代表
(i) 键
(ii) 含至 4 个碳原子的亚烷基或
(iii) 2 至 4 个碳原子的烯基(但不包括 α-CH=CHCH2β 和 αCH2CH=CHCH2β )、
R2b 代表 3
(i) 氢原子
(ii) 卤素原子或
(iii) 含 1 至 4 个碳原子的烷基、
通式(B)中 Cs 与 Cs 之间双键的构型为顺式、
代表
或
Lc 代表 1 至 4 个碳原子的亚烷基。R2c 代表氢原子、1 至 4 个碳原子的烷基或卤素原子、
通式(c)中 Cs 与 Cs 之间双键的构型为顺式或反式,但当
代表通式(A)时,R "不代表氢原子或 1 至 20 个碳原子的烷基;
在 R11 代表氢原子或 NR13R14 代表氨基酸残基的情况下,它们的环糊精凝块或无毒盐具有拮抗 TXA2 的活性,特别是抑制血小板聚集和动脉收缩,因此可用于预防和/或治疗心血管疾病、因此,可用于预防和/或治疗由血栓素 A2 引起的哺乳动物(尤其是人类)的炎症、高血压、血栓、脑中风、哮喘、心肌梗塞、心绞痛、脑梗塞和心脏病死亡。