Bioisosteric replacement of the pyrazole 3-carboxamide moiety of rimonabant. A novel series of oxadiazoles as CB1 cannabinoid receptor antagonists

Org Biomol Chem. 2008 Sep 21;6(18):3399-407. doi: 10.1039/b807648k. Epub 2008 Jul 23.

Abstract

Based on the bioisosteric replacement of the pyrazole C3-carboxamide of rimonabant with a 5-alkyl oxadiazole ring, a novel class of oxadiazole derivatives with promising biological activity towards CB1 receptors was discovered. Among them, compounds with an alkyl linker containing a strong electron-withdrawing group (e.g., CF(3)) and a sterically favorable bulky group (e.g., t-butyl) exhibited excellent CB1 antagonism and selectivity, and thus might serve as potential candidates for further development as anti-obesity agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / metabolism*
  • Cell Line
  • Humans
  • Isomerism
  • Molecular Structure
  • Piperidines / chemistry*
  • Piperidines / metabolism*
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Rimonabant
  • Structure-Activity Relationship

Substances

  • Amides
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • pyrazole
  • Rimonabant