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J Med Chem. 2004 Mar 11;47(6):1575-86.

Structure-activity relationships of potent, selective inhibitors of neuronal nitric oxide synthase based on the 6-phenyl-2-aminopyridine structure.

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Pfizer Global Research and Development, Pfizer Inc., Eastern Point Road, Groton Connecticut 06340, USA.


The synthesis and structure-activity relationships of a series of 6-phenyl-2-aminopyridines that potently and selectively inhibit the neuronal isoform of nitric oxide synthase (nNOS) are described. Compound 14bi from this series exhibits potent in vivo activity in harmaline-induced cGMP formation in rat cerebellum, a functional model of nNOS inhibition, and in the PCP-induced hypermotility model in the rat. These results suggest that 14bi may be a useful reagent for evaluating potential therapeutic applications of nNOS inhibitors in the central nervous system.

[Indexed for MEDLINE]

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