The Discovery and Development of HCV NS3 Protease Inhibitor Paritaprevir

Abstract

Hepatitis C virus (HCV) NS3/4A protease inhibitors play an important role in several of the combination regimens that have revolutionized the treatment of this disease, offering patients an excellent chance for a complete cure. Starting from inhibitors incorporating oxime-based P*-shelf moieties, a collaborative effort between Abbott Laboratories and Enanta Pharmaceuticals generated ABT-450 (paritaprevir, a component of Technivie™ and Viekira Pak™), incorporating novel P*-phenanthridine and P3-amide capping groups and pharmacokinetically boosted by ritonavir. The discovery and development of ABT-450 enabled one of the first IFN-free combination therapies for HCV genotype 1 infection and contributed to the transformation of the treatment of this chronic and deadly disease.