Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors  

作　　者：Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie Wen-Xia Zhou 

机构地区：[1]Beijing Institute of Pharmacology and Toxicology,Beijing,100850,China

出　　处：《Chinese Chemical Letters》2016年第10期1626-1629,共4页中国化学快报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81172924);Beijing Municipal Natural Science Foundation(No.7112106)

摘　　要：By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.

关 键 词：Alzheimer＇s diseaseBACE inhibitor SecretaseDrug discoveryCyclic acylguanidine 

分 类 号：TQ460.1[化学工程—制药化工]