Identification of a series of 1,3,4-trisubstituted pyrazoles as novel hepatitis C virus entry inhibitors

Abstract

In this report we describe the identification of novel pyrazole analogs as potent hepatitis C virus (HCV) entry inhibitor. The pyrazoles were identified by our phenotypic high-throughput screening using infectious HCV. A series of pyrazole derivatives was synthesized and evaluated for inhibitory activity against HCV in the infectious cell culture system. Through evaluation of selected compounds we observed that the pyrazoles did not interfere with HCV RNA replication but with viral entry as shown by experiments with HCV replicons and HCV pseudo particles, respectively.

Keywords: Entry inhibitor; Hepatitis C virus; Infectious cell culture system; Phenotypic high-throughput screening; Pyrazole.