2. Academic Validation
  3. Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors

Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors

  • Bioorg Med Chem Lett. 2009 Apr 15;19(8):2295-8. doi: 10.1016/j.bmcl.2009.02.079.
Salvatore Avolio 1,  Keith Robertson,  Josè Ignacio Martin Hernando,  Jillian DiMuzio,  Vincenzo Summa
Affiliations

Affiliation

  • 1 IRBM-Merck Research Laboratories Rome, Pomezia, Rome, Italy. salvatore_avolio@merck.com
PMID: 19285390 DOI: 10.1016/j.bmcl.2009.02.079
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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