A new class of selective and potent inhibitors of neuronal nitric oxide synthase

J A Lowe 3rd; W Qian; R A Volkmann; S Heck; J Nowakowski; R Nelson; C Nolan; D Liston; K Ward; S Zorn; C Johnson; M Vanase; W S Faraci; K A Verdries; J Baxter; S Doran; M Sanders; M Ashton; P Whittle; M Stefaniak

doi:10.1016/s0960-894x(99)00432-1

A new class of selective and potent inhibitors of neuronal nitric oxide synthase

Bioorg Med Chem Lett. 1999 Sep 6;9(17):2569-72. doi: 10.1016/s0960-894x(99)00432-1.

Authors

Affiliation

¹ Central Research Division, Pfizer Inc. Groton, CT 06340, USA.

PMID: 10498210
DOI: 10.1016/s0960-894x(99)00432-1

Abstract

The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity.

MeSH terms

Aminopyridines / chemical synthesis*
Aminopyridines / pharmacokinetics
Aminopyridines / pharmacology
Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology
Half-Life
Nitric Oxide Synthase / antagonists & inhibitors*
Nitric Oxide Synthase Type I
Rats
Structure-Activity Relationship

Substances

Aminopyridines
Enzyme Inhibitors
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nos1 protein, rat