Discovery of a series of aminopiperidines as novel iNOS inhibitors

Bertrand Le Bourdonnec, Lara K. Leister, Christopher A. Ajello, Joel A. Cassel, Pamela R. Seida, Heather O'Hare, Minghua Gu, Guo Hua Chu, Paul A. Tuthill, Robert N. DeHaven, Roland E. Dolle

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.

Original languageEnglish
Pages (from-to)336-343
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • Aminopiperidines
  • Inhibitors
  • iNOS

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    Bourdonnec, B. L., Leister, L. K., Ajello, C. A., Cassel, J. A., Seida, P. R., O'Hare, H., Gu, M., Chu, G. H., Tuthill, P. A., DeHaven, R. N., & Dolle, R. E. (2008). Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorganic and Medicinal Chemistry Letters, 18(1), 336-343. https://doi.org/10.1016/j.bmcl.2007.10.073