title: Bioisosteric replacement of the hydrazide pharmacophore of the cannabinoid-1 receptor antagonist SR141716A. Part I: potent, orally-active 1,4-disubstituted imidazoles.
abstract: A new series of CB(1) receptor antagonists incorporating an imidazole-based isosteric replacement for the hydrazide moiety of rimonabant (SR141716) is disclosed. Members of this imidazole series possess potent/selective binding to the rCB(1) receptor and exhibit potent hCB(1) functional activity. Isopropyl analog 9a demonstrated activity in the tetrad assay and was orally-active in a food intake model.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA. robert.l.dow@pfizer.com
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dow
authors.forename: John R
authors.initials: JR
authors.lastname: Hadcock
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Scott
authors.forename: Steven R
authors.initials: SR
authors.lastname: Schneider
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Paight
authors.forename: Philip A
authors.initials: PA
authors.lastname: Iredale
authors.forename: Philip A
authors.initials: PA
authors.lastname: Carpino
authors.forename: David A
authors.initials: DA
authors.lastname: Griffith
authors.forename: Marlys
authors.initials: M
authors.lastname: Hammond
authors.forename: Paul
authors.initials: P
authors.lastname: Dasilva-Jardine
mesh_terms: D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000077285:Rimonabant; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant