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Inhibitors of hepatitis C virus NS3.4A protease. Part 3: P2 proline variants.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2004 Apr 19; Vol. 14 (8), pp. 1939-42. - Publication Year :
- 2004
-
Abstract
- We recently described the identification of an optimized alpha-ketoamide warhead for our series of HCV NS3.4A inhibitors. We report herein a series of HCV protease inhibitors incorporating 3-alkyl-substituted prolines in P(2). These compounds show exceptional enzymatic and cellular potency given their relatively small size. The marked enhancement of activity of these 3-substituted proline derivatives relative to previously reported 4-hydroxyproline derivatives constitutes additional evidence for the importance of the S(2) binding pocket as the defining pharmacophore for inhibition of the NS3.4A enzyme.
- Subjects :
- Hepatitis C enzymology
Intracellular Signaling Peptides and Proteins
Models, Molecular
Molecular Structure
Oligopeptides chemical synthesis
Oligopeptides chemistry
Proline chemical synthesis
Proline chemistry
Structure-Activity Relationship
Carrier Proteins antagonists & inhibitors
Oligopeptides pharmacology
Proline pharmacology
Viral Nonstructural Proteins antagonists & inhibitors
Viral Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0960-894X
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 15050632
- Full Text :
- https://doi.org/10.1016/j.bmcl.2004.01.078