Document Detail


SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase.
MedLine Citation:
PMID:  16451069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemical potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases. The structures of the complexes formed between several of these inhibitors and HCV NS5b were determined by X-ray crystallography, and the inhibitors were found to bind in an allosteric binding site separate from the active site. Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b.
Authors:
Jay P Powers; Derek E Piper; Yang Li; Veronica Mayorga; John Anzola; James M Chen; Juan C Jaen; Gary Lee; Jinqian Liu; M Greg Peterson; George R Tonn; Qiuping Ye; Nigel P C Walker; Zhulun Wang
Related Documents :
18276139 - Substituted 2,2-bisaryl-bicycloheptanes as novel and potent inhibitors of 5-lipoxygenas...
19775099 - Design, synthesis, biological evaluation, and nmr studies of a new series of arylsulfon...
9113329 - Synthesis of indolylalkoxyiminoalkylcarboxylates as leukotriene biosynthesis inhibitors.
20074949 - N-acetamideindolecarboxylic acid allosteric 'finger-loop' inhibitors of the hepatitis c...
19059779 - Discovery of a novel series of quinoxalines as inhibitors of c-met kinase.
12750019 - The design of potent, non-peptidic inhibitors of hepatitis c protease.
11807949 - Crystal structure of non-allosteric l-lactate dehydrogenase from lactobacillus pentosus...
23109179 - Cation-π interactions in β-lactamases: the role in structural stability.
8953379 - Modification of domains of alpha and beta subunits of f1-atpase from the thermophylic b...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  49     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-02     Completed Date:  2006-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1034-46     Citation Subset:  IM    
Affiliation:
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. jppowers@amgen.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Allosteric Site
Avian myeloblastosis virus / enzymology
Binding Sites
Crystallography, X-Ray
DNA-Directed RNA Polymerases / antagonists & inhibitors*,  chemistry*
Diarrhea Viruses, Bovine Viral / enzymology
Models, Molecular*
Protein Conformation
Reverse Transcriptase Inhibitors / chemical synthesis,  chemistry
Structure-Activity Relationship
Thiazoles / chemical synthesis*,  chemistry
Thiones / chemical synthesis*,  chemistry
Viral Nonstructural Proteins / antagonists & inhibitors*,  chemistry*
Chemical
Reg. No./Substance:
0/NS-5 protein, hepatitis C virus; 0/Reverse Transcriptase Inhibitors; 0/Thiazoles; 0/Thiones; 0/Viral Nonstructural Proteins; EC 2.7.7.6/DNA-Directed RNA Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Docking of aminoglycosides to hydrated and flexible RNA.
Next Document:  GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose-dependent insulinot...