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Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors
Salvatore Avolio1, Keith Robertson, Josè Ignacio Martin Hernando
1IRBM-Merck Research Laboratories Rome, Pomezia, Rome, Italy. salvatore_avolio@merck.com
Abstract:
A novel series of hepatitis C virus (HCV) NS3/4A protease inhibitors bearing a P2-P4 macrocycle and a P1-P1' alpha-ketoamide serine trap is reported. The NS3 protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. The optimization of both the macrocycle and the warhead portions led to the discovery of compounds 8b and 8 g with a good activity both in the enzyme as well as in the cell based (replicon) assays with favorable PK profile in a preclinical species.
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