Design and synthesis of phenylisoxazole derivatives as novel human acrosin inhibitors

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• 作者：Juntao Zhao^&dagger ; ; Wei Tian^&dagger ; ; Jingjing Qi^&dagger ; ; Diya Lv ; Yang Liu ; Yan Jiang ; Guoqiang Dong ; Qianqian Chen ; Youjun Zhou ; Ju Zhu ; Heling Wang ; Chunquan Sheng ; ^{shengcq@hotmail.com" class="auth_mail} ; Jiaguo Lv ; ^{ljg19580808@163.com" class="auth_mail}
• 关键词：Guanidinophenylpyrazole derivatives ; Molecular hybridization ; Male contraceptive ; Human acrosin inhibitors
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：1 July 2014
• 年：2014
• 卷：24
• 期：13
• 页码：2802-2806
• 全文大小：3478 K

文摘

Human acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC₅₀ = 1.44 渭M) was successfully identified, which showed good selectivity over trypsin and represents one of the most active human acrosin inhibitors up to date.