甲基在药物分子设计中的应用  

Application of methyl in drug design

作　　者：连捷[1,2] 王江[2] 孙海峰[2] 林岱宗[2] 柳红[1,2] 

机构地区：[1]中国药科大学药学院,江苏南京210009 [2]中国科学院上海药物研究所,新药研究国家重点实验室,上海201203

出　　处：《药学学报》2013年第8期1195-1208,共14页Acta Pharmaceutica Sinica

摘　　要：甲基在药物分子的合理设计中起到重要作用,如何巧妙地在分子中引入甲基已成为先导化合物结构优化的重要改造策略之一。本文综述了在药物分子设计中一些合理引入甲基的应用实例。将甲基引入小分子中通过影响脂溶性和水溶性改变药物的理化性质;通过诱导效应、改变分子构象以及改变蛋白配体相互作用影响药物的药效性质;通过邻位效应、弱代谢作用以及增加稳定性来影响药物的代谢性质;同时,甲基在me-too药物研发以及老药新用研发策略中也起到重要作用。The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.

关 键 词：甲基 药物设计 结构优化 空间电子效应 脂溶性 

分 类 号：R916[医药卫生—药学]