Design and synthesis of 2-aminobenzimidazoles as potential BACE1 inhibitors

作     者：Jiapei Yu Yan Niu Qi Sun Fengrong Xu Lei Liang Chao Wang Ping Xu 余家沛;牛彦;孙琦;许凤荣;梁磊;王超;徐萍

作者机构：Department of Medicinal Chemistry School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100191 China 

基　　金：National Natural Science Foundation of China(Grant No.21002002/21172012) 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2017年第26卷第9期

页      码：650-659页

摘      要：Fragment-based drug discovery （FBDD） has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad （Asp228 and Asp32） of D-site amyloid precursor protein cleaving enzyme 1 （BACE1）. A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 pM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/$2＇ pockets well.

主 题 词：Alzheimer's disease BACE1 inhibitors FBDD 2-Aminobenzimidazole 

学科分类：1007[医学-药学类] 100701[100701] 10[医学] 

核心收录：

D　O　I：10.5246/jcps.2017.09.073

馆 藏 号：203267389...