Discovery and functional evaluation of diverse novel human CB(1) receptor ligands

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4183-90. doi: 10.1016/j.bmcl.2009.05.114. Epub 2009 Jun 2.

Abstract

Ligand-based virtual screening with a 3D pharmacophore led to the discovery of 30 novel, diverse and drug-like ligands of the human cannabinoid receptor 1 (hCB(1)). The pharmacophore was validated with a hit rate of 16%, binding selectivity versus hCB(2), and expected functional profiles. The discovered compounds provide new tools for exploring cannabinoid pharmacology.

MeSH terms

  • Animals
  • Cannabinoids / chemistry
  • Cannabis / metabolism
  • Chemistry, Pharmaceutical / methods*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Mice
  • Models, Chemical
  • Molecular Structure
  • Obesity / drug therapy
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / chemistry
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Rimonabant

Substances

  • Cannabinoids
  • Ligands
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Rimonabant