Synthesis and acrosin inhibitory activity of methyl 5-substituted-1H-benzo[d]imidazol-2-yl carbamate derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 10; pp. 3554 - 3559
• Main Authors: Liu, Xuefei, Chen, Qianqian, Zhu, Ju, Fan, Yongzheng, Ding, Lili, Zhao, Juntao, Han, Guangqian, Tian, Wei, Qi, Jingjing, Zhou, Youjun, Lv, Jiaguo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.05.2012
• Subjects: acrosin; Acrosin - antagonists & inhibitors; acrosin inhibitory agents; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; chemistry; inhibitory concentration 50; Magnetic Resonance Spectroscopy; Mass Spectrometry; methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamate; Models, Molecular; synthesis; synthesis; methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamate; acrosin inhibitory agents
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.03.042

A series of new methyl 5-substituted-1H-benzo[d]imidazol-2-yl carbamate derivatives were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4w being significantly more potent than the control compound N-alpha-tosyl-L-lysyl-chloromethyl-ket one (TLCK). The docking results of compounds 4w in the active site of acrosin are also shown. A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acrosin inhibitory activity among all the compounds, with an IC50 of 6.3×10−5M. The studies provide a new structural class for the development of novel acrosin inhibitory agents.