选择性毒蕈碱受体激动剂的研究

Recent Progress in Selective Muscarinic Agonists

随着毒蕈碱受体 (M受体 )亚型及能甄别这些受体亚型的化合物的不断发现 ,为寻找新型、高效、选择性高且副作用小的用于治疗阿尔茨海默病的M受体激动剂提供了理论依据。综述选择性M受体激动剂槟榔碱及其衍生物的结构修饰、构效关系以及临床研究新进展 ,其中结构改造主要包括四氢吡啶环的单或双氮杂环取代及以肟醚基、醚基或五元杂环作为生物电子等排体取代酯基。

The discovery of muscarinic receptor subtypes and subtype-preferring compounds has promoted the development of new, potent, highly selective and adverse effect-lowering muscarinic agonists. This review described the recent progress in the structural modification, structure -activity relationship and clinical development of arecoline derivatives , including the replacement of tetrahydropyridine ring by other monocyclic or bicyclic aza rings and the replacement of ester group by oxime ethers, ethers or five-membered heterocyclic rings as ester bioisosteres.