作为H1抗组胺剂的一系列新型苯并咪唑的合成及其构效关系
Synthesis and structure-activity relationships of a new series of benzimidazoles as H1-antihistaminic agents.
作者信息
Cuberes M R, Contijoch M, Calvet C, Alegre J, Quintana J R, Frigola J
机构信息
Department of Medicinal Chemistry, Laboratorios Dr. Esteve, S. A., Barcelona, Spain.
出版信息
Chem Pharm Bull (Tokyo). 1997 Aug;45(8):1287-92. doi: 10.1248/cpb.45.1287.
New 2-(4-(4-azolylbutyl)piperazinyl)-, 2-(4-(4-azolylbutyl) piperazinylmethyl)-, 2-(4-(-azolylbutyl)homopiperazinyl)- and 2-(4-(4-azolylbutyl)homopiperazinylmethyl)benzimidazoles were synthesized, characterized and tested for in vitro and in vivo H1-antihistaminic activity. Structure-activity relationships implied that the best antihistaminic activity required the simultaneous presence of a homopiperazinylbenzimidazole system (or a methylene linker between the benzimidazole and the piperazine rings) and an unsubstituted pyrazole ring. 1-(2-Ethoxyethyl)-2-¿4-[4-(pyrazol-1-yl)butyl] homopiperazin-1-yl¿benzimidazole (17), as its dimaleate salt, has been chosen for further development.
合成了新型的2-(4-(4-唑基丁基)哌嗪基)-、2-(4-(4-唑基丁基)哌嗪基甲基)-、2-(4-(唑基丁基)高哌嗪基)-和2-(4-(4-唑基丁基)高哌嗪基甲基)苯并咪唑，并对其进行了表征及体外和体内H1抗组胺活性测试。构效关系表明，最佳抗组胺活性需要同时存在高哌嗪基苯并咪唑体系（或苯并咪唑与哌嗪环之间的亚甲基连接基）和未取代的吡唑环。已选择1-(2-乙氧基乙基)-2-[4-[4-(吡唑-1-基)丁基]高哌嗪-1-基]苯并咪唑（17）的二马来酸盐进行进一步研发。
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