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ID: ALA2311372

Journal: Eur J Med Chem

Title: Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.

Authors: Chen Q, Tian W, Han G, Qi J, Zheng C, Zhou Y, Ding L, Zhao J, Zhu J, Lv J, Sheng C.

Abstract: Human acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized. Most of the synthesized compounds showed potent human acrosin inhibitory activity and their binding modes were investigated by molecular docking. The scaffold of the compounds was found to be important for the inhibitory activity. Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.

CiteXplore: 23220646

DOI: 10.1016/j.ejmech.2012.11.005