Synthesis and acrosin inhibitory activities of substituted ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 19; pp. 5822 - 5825
• Main Authors: Qi, Jingjing, Zhu, Ju, Liu, Xuefei, Ding, Lili, Zheng, Canhui, Han, Guangqian, Lv, Jiaguo, Zhou, Youjun
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.10.2011; Elsevier
• Subjects: acrosin; Acrosin - antagonists & inhibitors; Biological and medical sciences; carboxylic acids; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Contraceptive Agents - chemical synthesis; Contraceptive Agents - chemistry; Contraceptive Agents - pharmacology; Drug Design; enzyme inhibition; enzyme inhibitors; Fertilization - physiology; Genital system. Reproduction; Humans; Male; Medical sciences; Molecular Targeted Therapy; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Serine Proteinase Inhibitors - chemical synthesis; Serine Proteinase Inhibitors - chemistry; Serine Proteinase Inhibitors - pharmacology; Software; Structure-Activity Relationship; structure-activity relationships; Tosyllysine Chloromethyl Ketone - chemistry; Tosyllysine Chloromethyl Ketone - metabolism; Tosyllysine Chloromethyl Ketone - pharmacology; Serine endopeptidases; Acrosin inhibitory agents; Enzyme; Ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate; Acrosin; Enzyme inhibitor; Inhibitor enzyme complex; In vitro; Modeling; Biological activity; Peptidases; Synthesis; Chlorine Organic compounds; Molecular model; Pyrazole derivatives; Binding mode; Hydrolases; Carboxamide; Benzamide derivatives; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.07.110

A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the control TLCK. These provide a new structural type for the development of novel contraceptive acrosin inhibitory agents.