Telaprevir (Incivek) and Boceprevir (Victrelis): NS3/4A Inhibitors for Treatment for Hepatitis C Virus (HCV)

The discovery and development efforts that led to successful approval of boceprevir and telaprevir have produced tangible benefits to Hepatatis C virus (HCV) patients worldwide. Meta-analyses designed to compare the efficacy and safety of boceprevir and telaprevir have been reported. In order to address the challenging substrate-binding site of HCV NS3/4A, a number of research teams have explored the design of reversible, covalent inhibitors. This strategy, which produced drug candidates for other protease inhibitors, involves incorporation of an electrophilic trap, or “warhead”, into a substrate-like inhibitor. This chapter presents, among other things, a few key aspects of SAR studies for boceprevir and telaprevir. It also discusses the various approaches for the synthesis of boceprevir and telaprevir.