Inhibitors of hepatitis C virus NS3.4A protease 2. Warhead SAR and optimization

Robert B Perni; Janos Pitlik; Shawn D Britt; John J Court; Lawrence F Courtney; David D Deininger; Luc J Farmer; Cynthia A Gates; Scott L Harbeson; Rhonda B Levin; Chao Lin; Kai Lin; Young-Choon Moon; Yu-Ping Luong; Ethan T O'Malley; B Govinda Rao; John A Thomson; Roger D Tung; John H Van Drie; Yunyi Wei

doi:10.1016/j.bmcl.2004.01.022

Inhibitors of hepatitis C virus NS3.4A protease 2. Warhead SAR and optimization

Bioorg Med Chem Lett. 2004 Mar 22;14(6):1441-6. doi: 10.1016/j.bmcl.2004.01.022.

Affiliation

¹ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA.

PMID: 15006379
DOI: 10.1016/j.bmcl.2004.01.022

Abstract

The alpha-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3.4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed.

MeSH terms

Carbamates / chemistry
Carbamates / metabolism
Hepacivirus / drug effects
Hepacivirus / enzymology*
Macrocyclic Compounds*
Quinolines*
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemistry*
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / metabolism
Viral Nonstructural Proteins / antagonists & inhibitors*
Viral Nonstructural Proteins / metabolism

Substances

BILN 2061
Carbamates
Macrocyclic Compounds
NS3 protein, hepatitis C virus
NS4 protein, hepatitis C virus
Quinolines
Serine Proteinase Inhibitors
Thiazoles
Viral Nonstructural Proteins
Serine Endopeptidases