Synthesis and enzymatic evaluation of 2- and 4-aminothiazole-based inhibitors of neuronal nitric oxide synthase

Graham R. Lawton, Haitao Ji, Pavel Martásek, Linda J. Roman, Richard B. Silverman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Highly potent and selective inhibitors of neuronal nitric oxide synthase (nNOS) possessing a 2-aminopyridine group were recently designed and synthesized in our laboratory and were shown to have significant in vivo efficacy. In this work, analogs of our lead compound possessing 2- and 4-aminothiazole rings in place of the aminopyridine were synthesized. The less basic aminothiazole rings will be less protonated at physiological pH than the aminopyridine ring, and so the molecule will carry a lower net charge. This could lead to an increased ability to cross the blood-brain barrier thereby increasing the in vivo potency of these compounds. The 2-aminothiazole-based compound was less potent than the 2-aminopyridine-based analogue. 4-Aminothiazoles were unstable in water, undergoing tautomerization and hydrolysis to give inactive thiazolones.

Original languageEnglish (US)
Article number28
JournalBeilstein Journal of Organic Chemistry
Volume5
DOIs
StatePublished - Jun 4 2009

Keywords

  • 2-aminothiazole
  • 4-aminothiazole
  • NNOS
  • Nitric oxide synthase inhibitor

ASJC Scopus subject areas

  • Organic Chemistry

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