16-Hydroxy-16-vinyl (or cyclopropyl)-prostan-1-ols and pharmaceutical compositions containing the same
申请人:AMERICAN CYANAMID COMPANY
公开号:EP0013107A1
公开(公告)日:1980-07-09
There are disclosed novel 15-deoxy-16-hydroxy-16- substituted prostanoic acid analogs in which the C-1 carboxyl is replaced by a primary alcohol and carboxylic acid esters, carbonates and carbamates thereof, and which have utility as bronchodilators, as hypotensive agents, and as agents forthe control of excessive gastric secretion. The novel compounds are represented by the formula:
wherein Q is a divalent cyclopentyl moiety selected from the group consisting of:
wherein R/ is an alkyl (C3-C7) optionally substituted with one or more alkyl groups of one to three carbon atoms; R2 is selected from the group hydroxyl, alkoxyl, alkanoyloxy, a protecting group such as tetrahydropyran-2-yl-oxy, triloweralkylsilyloxy; or alkoxyalkoxy such as
wherein R' is hydrogen or alkyl (C1-C4) and R" is alkyl (C1-C4); X is the divalent radical
wherein R3 is selected from the group vinyl and cyclopropyl; Z is selected from the group -(CH2)4, cis and
and W is selected from the group consisting of -(CH2)3 OH and
wherein R4 is selected from the group alkyl (C,-C.); alkoxy (C1-C4); dialkylamino (C1-C4); phenyl and phenyl substituted with one or more substituents selected from the group consisting of hydrogen, hydroxyl, lower alkyl, lower alkoxy, loweralkylthia, fluoride or chloride, wherein lower alkyl is C1-C4; The formula above embraces the optical isomers, racemic or other mixtures of these isomers and the mirror images thereof
公开了新型 15-脱氧-16-羟基-16-取代的前列酸类似物,其中 C-1 羧基被伯醇及其羧酸酯、碳酸酯和氨基甲酸酯取代,可用作支气管扩张剂、降压药和控制胃分泌过多的药物。这些新型化合物由式表示:
其中 Q 是二价环戊基,选自由以下组成的组:
其中 R/ 是任选被一个或多个一至三个碳原子的烷基取代的烷基(C3-C7);R2 选自羟基、烷氧基、烷酰氧基、保护基团如四氢吡喃-2-基氧基、三烷基硅氧基;或烷氧基烷氧基,如
其中 R' 为氢或烷基(C1-C4),R" 为烷基(C1-C4); X 为二价基
其中 R3 选自乙烯基和环丙基组; Z 选自-(CH2)4 组,顺式和逆式。
和 W 选自-(CH2)3 OH 和-(CH2)4-OH 所组成的组。
其中 R4 选自烷基(C,-C.);烷氧基(C1-C4);二烷基氨基(C1-C4);苯基和被一个或多个取代基取代的苯基,取代基选自氢、羟基、低级烷基、低级烷氧基、低级烷硫基、氟化物或氯化物组成的组,其中低级烷基为 C1-C4; 上式包括这些异构体的光学异构体、外消旋体或其他混合物及其镜像。