Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus

Abstract

A series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC₅₀ values almost equivalent to the clinical drug telaprevir (EC₅₀ = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in rats: 34%) profile, suggesting a highly drug-like nature. Compound 80represents a more promising scaffold for anti-HCV virus activity for further study.

Keywords: Biaryl amide; HCV; Nitro group; Pharmacokinetics; Structure-activity relationship; hA3G.