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.
Date:
2010-09-01
Relation:
Bioorganic and Medicinal Chemistry. 2010 Sep ;18(17):6414-6421.
