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Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 May 01; Vol. 23 (9), pp. 2585-9. Date of Electronic Publication: 2013 Mar 07. - Publication Year :
- 2013
-
Abstract
- A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment-based approach using information from X-ray crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of parallel synthesis. Structure-based drug design strategies led to the discovery of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment-like structure 1 as a starting point.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antiviral Agents chemical synthesis
Antiviral Agents pharmacology
Binding Sites
Caco-2 Cells
Cell Membrane Permeability drug effects
Crystallography, X-Ray
Drug Evaluation, Preclinical
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
Hepacivirus enzymology
Humans
Molecular Docking Simulation
Nucleosides chemistry
Protein Structure, Tertiary
Structure-Activity Relationship
Viral Nonstructural Proteins metabolism
ortho-Aminobenzoates chemistry
Antiviral Agents chemistry
Enzyme Inhibitors chemistry
Hepacivirus drug effects
Viral Nonstructural Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 23
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23545108
- Full Text :
- https://doi.org/10.1016/j.bmcl.2013.02.110