Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase

Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1 H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacteri...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-05, Vol.20 (9), p.2828-2831
Main Authors: Ronkin, Steven M., Badia, Michael, Bellon, Steve, Grillot, Anne-Laure, Gross, Christian H., Grossman, Trudy H., Mani, Nagraj, Parsons, Jonathan D., Stamos, Dean, Trudeau, Martin, Wei, Yunyi, Charifson, Paul S.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibacterials
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial gyrase
Binding Sites
Biological and medical sciences
Crystallography, X-Ray
DNA Gyrase - metabolism
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Escherichia coli
Medical sciences
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Structure-Activity Relationship
Thiazoles - chemical synthesis
Thiazoles - chemistry
Thiazoles - pharmacology
Topoisomerase II Inhibitors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1 H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphlococcus aureus GyrB.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.03.052