The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)

David R Cheshire; Anders Åberg; Gunilla M K Andersson; Glen Andrews; Haydn G Beaton; Timothy N Birkinshaw; Nigel Boughton-Smith; Stephen Connolly; Tony R Cook; Anne Cooper; Sally L Cooper; David Cox; John Dixon; Nigel Gensmantel; Peter J Hamley; Richard Harrison; Paul Hartopp; Helena Käck; Paul D Leeson; Timothy Luker; Antonio Mete; Ian Millichip; David J Nicholls; Austen D Pimm; Steve A St-Gallay; Alan V Wallace

doi:10.1016/j.bmcl.2011.02.061

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2468-71. doi: 10.1016/j.bmcl.2011.02.061. Epub 2011 Feb 18.

Affiliation

¹ Department of Chemistry, AstraZeneca Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom. dave.cheshire@astrazeneca.com

PMID: 21398123
DOI: 10.1016/j.bmcl.2011.02.061

Abstract

By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.

MeSH terms

Animals
Binding Sites
Computer Simulation
Crystallography, X-Ray
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Isoxazoles / chemical synthesis
Isoxazoles / chemistry*
Isoxazoles / pharmacology
Mice
Microsomes, Liver / metabolism
Nitric Oxide Synthase Type II / antagonists & inhibitors*
Nitric Oxide Synthase Type II / metabolism
Protein Structure, Tertiary
Pyridines / chemistry*
Pyridines / pharmacology
Rats

Substances

Enzyme Inhibitors
Isoxazoles
Pyridines
Nitric Oxide Synthase Type II