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Potent and selective conformationally restricted neuronal nitric oxide synthase inhibitors.

Abstract：

:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we report conformationally restricted dipeptides derived from the dipeptide L-Arg(NO2)-L-Dbu-NH2 (8). The selectivities for nNOS over endothelial NOS and inducible NOS of the most potent nNOS inhibitor (10a) among these compounds are comparable to that of the parent compound. An unsubstituted amide bond is necessary for potency against nNOS. The stereochemistry of compound 10a was optimum for potency and selectivity and thus provides the binding conformation of the parent compound with nNOS.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

doi

10.1021/jm030297m

keywords:

subject

Has Abstract

pub_date

2004-01-29 00:00:00

pages

703-10

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

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