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

Fengtian Xue, James M. Kraus, Kristin Jansen Labby, Haitao Ji, Jan Mataka, Guoyao Xia, Huiying Li, Silvia L. Delker, Linda J. Roman, Pavel Martásek, Thomas L. Poulos, Richard B. Silverman

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6399-6403
Number of pages5
JournalJournal of Medicinal Chemistry
Volume54
Issue number18
DOIs
StatePublished - Sep 22 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Xue, F., Kraus, J. M., Labby, K. J., Ji, H., Mataka, J., Xia, G., Li, H., Delker, S. L., Roman, L. J., Martásek, P., Poulos, T. L., & Silverman, R. B. (2011). Improved synthesis of chiral pyrrolidine inhibitors and their binding properties to neuronal nitric oxide synthase. Journal of Medicinal Chemistry, 54(18), 6399-6403. https://doi.org/10.1021/jm200411j