Orally active indole N-oxide PDE4 inhibitors

Christopher Hulme, Rose Mathew, Kevin Moriarty, Bruce Miller, Mercy Ramanjulu, Paul Cox, John Souness, Ken M. Page, Joanne Uhl, Jeffrey Travis, Richard Labaudiniere, Fu Chih Huang, Stevan W. Djuric

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-α levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.

Original languageEnglish (US)
Pages (from-to)3053-3058
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume8
Issue number21
DOIs
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Hulme, C., Mathew, R., Moriarty, K., Miller, B., Ramanjulu, M., Cox, P., Souness, J., Page, K. M., Uhl, J., Travis, J., Labaudiniere, R., Huang, F. C., & Djuric, S. W. (1998). Orally active indole N-oxide PDE4 inhibitors. Bioorganic and Medicinal Chemistry Letters, 8(21), 3053-3058. https://doi.org/10.1016/S0960-894X(98)00572-1