Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists

Takao Kiyoi, Julia M Adam, John K Clark, Keneth Davies, Anna-Marie Easson, Darren Edwards, Helen Feilden, Ruth Fields, Stuart Francis, Fiona Jeremiah, Duncan McArthur, Angus J Morrison, Alan Prosser, Paul D Ratcliffe, Jurgen Schulz, Grant Wishart, James Baker, Robert Campbell, Jean E Cottney, Maureen DeehanOla Epemolu, Louise Evans

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia.

Original languageEnglish
Pages (from-to)1748-1753
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number6
DOIs
Publication statusPublished - 15 Mar 2011

Keywords

  • administration, oral
  • animals
  • biological availability
  • drug discovery
  • heterocyclic compounds
  • rats
  • receptor, cannabinoid, CB1

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    Kiyoi, T., Adam, J. M., Clark, J. K., Davies, K., Easson, A-M., Edwards, D., Feilden, H., Fields, R., Francis, S., Jeremiah, F., McArthur, D., Morrison, A. J., Prosser, A., Ratcliffe, P. D., Schulz, J., Wishart, G., Baker, J., Campbell, R., Cottney, J. E., ... Evans, L. (2011). Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. Bioorganic and Medicinal Chemistry Letters, 21(6), 1748-1753. https://doi.org/10.1016/j.bmcl.2011.01.082