Structure-based design of hexahydropyrimidin-5-ols as novel non-peptidic β-secretase inhibitors  

六氢嘧啶-5-醇类新型非肽类β-分泌酶抑制剂的基于结构的药物分子设计(英文)

作　　者：周博[1] 牛彦[1] 邹晓民[1] 许凤荣[1] 袁悦[1] 王超[1] 高海飞[1] 刘鹏[1] 徐萍[1] 

机构地区：[1]北京大学医学部药学院药物化学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第5期341-345,共5页中国药学（英文版）

基　　金：National Natural Science Foundation of China (Grant No.20772008 and 30772650)

摘　　要：Based upon the crystal structure of a previously reported fragment hit that binds to Corresponding author. β-secretase, a novel series of non-peptidic small-molecule β-secretase inhibitors, namely hexahydropyrimidin-5-ols, along with two series of their analogues, were rationally designed through structural modification. The CADD study was performed and revealed good expectation. Inhibitory activities of the corresponding structural cores were tested, which provided further support for our design approach.本文由文献报道的已知小分子苗头化合物片段出发,基于其与β-分泌酶结合的晶体结构,通过结构修饰设计了全新的非肽类小分子β-分泌酶抑制剂:六氢嘧啶-5-醇系列及其两类类似物系列。计算机辅助药物设计的研究得到了良好的结果。我们测试了各类母核的β-分泌酶抑制活性,结果进一步支持了我们的设计思路。

关 键 词：β-Secretase inhibitors Hexahydropyrimidin-5-ols Structure-based drug design Computer-aided drug design 

分 类 号：R917[医药卫生—药物分析学]