中文摘要：

本文由文献报道的己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。

英文摘要：

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.