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Improved synthesis of chiral pyrrolidine inhibitors and their binding properties to neuronal nitric oxide synthase.

ABSTRACT: We report an efficient synthetic route to chiral pyrrolidine inhibitors of neuronal nitric oxide synthase (nNOS) and crystal structures of the inhibitors bound to nNOS and to endothelial NOS. The new route enables versatile structure-activity relationship studies on the pyrrolidine-based scaffold, which can be beneficial for further development of nNOS inhibitors. The X-ray crystal structures of five new fluorine-containing inhibitors bound to nNOS provide insights into the effect of the fluorine atoms on binding.

SUBMITTER: Xue F

PROVIDER: S-EPMC3174355 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Improved synthesis of chiral pyrrolidine inhibitors and their binding properties to neuronal nitric oxide synthase.

Xue Fengtian F Kraus James M JM Labby Kristin Jansen KJ Ji Haitao H Mataka Jan J Xia Guoyao G Li Huiying H Delker Silvia L SL Roman Linda J LJ Martásek Pavel P Poulos Thomas L TL Silverman Richard B RB

Journal of medicinal chemistry 20110822 18

We report an efficient synthetic route to chiral pyrrolidine inhibitors of neuronal nitric oxide synthase (nNOS) and crystal structures of the inhibitors bound to nNOS and to endothelial NOS. The new route enables versatile structure-activity relationship studies on the pyrrolidine-based scaffold, which can be beneficial for further development of nNOS inhibitors. The X-ray crystal structures of five new fluorine-containing inhibitors bound to nNOS provide insights into the effect of the fluorin ...[more]

PMID: 21809851

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Concise route to the chiral pyrrolidine core of selective inhibitors of neuronal nitric oxide.

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