目的基于人精子顶体酶活性位点的三维结构设计并合成新型3-取代喹唑啉酮类化合物。方法计算机模拟设计及化学合成。结果设计并合成了7个3-取代喹唑啉酮类先导物,进行了抑酶活性测试。结论所有合成的化合物具有较好的抑酶活性,其中化合物3 g是对照物Nα-对甲苯磺酰-L-赖氨酸氯甲基酮(TLCK)的229倍。 OBJECTIVE To design and synthesize novel 3-substituted quinazolinones based on the three-dimensional structure of human sperm acrosin active site. Methods Computer simulation design and chemical synthesis. Results Seven 3-substituted quinazolinone precursors were designed and synthesized, and their antimicrobial activities were tested. Conclusions All the synthesized compounds have good activity of inhibiting enzyme, of which compound 3 g is 229 times of the control Nα-p-toluenesulfonyl-L-lysine chloromethyl ketone (TLCK).