Synthesis, activity, and pharmacokinetic properties of a series of conformationally-restricted thiourea analogs as novel hepatitis C virus inhibitors

A series of novel conformationally-restricted thiourea analogs were designed, synthesized, and evaluated for their anti-HCV activity. Herein we report the synthesis, structure–activity relationships (SARs), and pharmacokinetic properties of this new class of thiourea compounds that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the fluorene compound 4b was found to possess the most potent activity (EC50 = 0.3 μM), lower cytotoxicity (CC50 > 50 μM), and significantly better pharmacokinetic properties compared to its corresponding fluorenone compound 4c.

A series of novel conformationally-restricted thiourea analogs were designed, synthesized, and evaluated for their anti-HCV activity and pharmacokinetic properties.Figure optionsDownload as PowerPoint slide