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Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Aug 15; Vol. 24 (16), pp. 3979-85. Date of Electronic Publication: 2014 Jun 20. - Publication Year :
- 2014
-
Abstract
- Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents chemical synthesis
Antiviral Agents chemistry
Carboxylic Acids chemical synthesis
Carboxylic Acids chemistry
Dogs
Dose-Response Relationship, Drug
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Hepacivirus drug effects
Hepacivirus enzymology
Lactams chemistry
Molecular Structure
RNA-Dependent RNA Polymerase metabolism
Rats
Structure-Activity Relationship
Thiophenes chemistry
Viral Nonstructural Proteins metabolism
Antiviral Agents pharmacology
Carboxylic Acids pharmacology
Drug Design
Enzyme Inhibitors pharmacology
RNA-Dependent RNA Polymerase antagonists & inhibitors
Viral Nonstructural Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 24
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 24986660
- Full Text :
- https://doi.org/10.1016/j.bmcl.2014.06.031