Abstract
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.
MeSH terms
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Aminopyridines / chemical synthesis*
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Aminopyridines / chemistry
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Aminopyridines / pharmacology
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Animals
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Cerebellum / drug effects
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Cerebellum / metabolism
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Cyclic GMP / biosynthesis
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Male
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Motor Activity / drug effects
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase / chemistry
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Nitric Oxide Synthase Type I
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Tetrahydronaphthalenes / chemical synthesis*
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Tetrahydronaphthalenes / chemistry
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Tetrahydronaphthalenes / pharmacology
Substances
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6-(4-(N,N-dimethylaminoethoxy)-5,6,7,8-tetrahydronaphthalen-1-yl)pyridin-2-ylamine
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Aminopyridines
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Tetrahydronaphthalenes
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Cyclic GMP