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J Med Chem. 2004 Jun 3;47(12):3320-3.

2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution.

Author information

1
Medicinal Chemistry, Discovery BioScience, Molecular Biology and Physical and Metabolic Sciences Departments, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics LE11 5RH, U.K. steve.connolly@astrazeneca.com

Abstract

4-Methylaminopyridine (4-MAP) (5) is a potent but nonselective nitric oxide synthase (NOS) inhibitor. While simple N-methylation in this series results in poor activity, more elaborate N-substitution such as with 4-piperidine carbamate or amide results in potent and selective inducible NOS inhibition. Evidently, a flipping of the pyridine ring between these new inhibitors allows the piperidine to interact with different residues and confer excellent selectivity.

PMID:
15163211
DOI:
10.1021/jm031035n
[Indexed for MEDLINE]

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