Discovery and functional evaluation of diverse novel human CB(1) receptor ligands.
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.
Foloppe
Nicolas
N
Vernalis (R&D) Ltd, Granta Park, Abington, Cambridge, CB21 6GB, UK. n.foloppe@vernalis.com
Benwell
Karen
K
Brooks
Teresa D
TD
Kennett
Guy
G
Knight
Antony R
AR
Misra
Anil
A
Monck
Nathaniel J T
NJ
D000818:Animals; D002186:Cannabinoids / Q000737:chemistry; D002188:Cannabis / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry / Q000378:metabolism*; D000077285:Rimonabant
D002186:Cannabinoids; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant