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Potent and selective neuronal nitric oxide synthase inhibitors with improved cellular permeability.

ABSTRACT: Recently, a series of potent and selective neuronal nitric oxide synthase inhibitors containing two basic nitrogen atoms was reported (Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. J. Am. Chem. Soc. 2008, 130, 3900-3914). In an effort to improve their bioavailability, three compounds (2a-c) were designed with electron-withdrawing groups near one of the basic nitrogen atoms to lower its pK(a). Inhibition studies with these compounds showed that two of them not only retained most of the potency and selectivity of the best analogue of the earlier series, but also showed improved membrane permeability based on data from a cell-based assay.

SUBMITTER: Xue F

PROVIDER: S-EPMC2818568 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Potent and selective neuronal nitric oxide synthase inhibitors with improved cellular permeability.

Xue Fengtian F Fang Jianguo J Lewis William W WW Martásek Pavel P Roman Linda J LJ Silverman Richard B RB

Bioorganic & medicinal chemistry letters 20091122 2

Recently, a series of potent and selective neuronal nitric oxide synthase inhibitors containing two basic nitrogen atoms was reported (Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. J. Am. Chem. Soc. 2008, 130, 3900-3914). In an effort to improve their bioavailability, three compounds (2a-c) were designed with electron-withdrawing groups near one of the basic nitrogen atoms to lower its pK(a). Inhibition studies with these compounds show ...[more]

PMID: 19963381

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