title: Synthesis and activity of 4,5-diarylimidazoles as human CB1 receptor inverse agonists.
abstract: Structure-activity relationship studies directed toward the optimization of 4,5-diarylimidazole-2-carboxamide analogs as human CB1 receptor inverse agonists resulted in the discovery of the two amide derivatives 24a and b (hCB1 IC50 = 6.1 and 4.0 nM) which also demonstrated efficacy in overnight feeding studies in the rat for reduction in both food intake and overall body weight.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. christopher_plummer@merck.com
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Plummer
authors.forename: Paul E
authors.initials: PE
authors.lastname: Finke
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: George A
authors.initials: GA
authors.lastname: Doss
authors.forename: Tung M
authors.initials: TM
authors.lastname: Fong
authors.forename: Julie Z
authors.initials: JZ
authors.lastname: Lao
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Schaeffer
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Chun-Pyn
authors.initials: CP
authors.lastname: Shen
authors.forename: D Sloan
authors.initials: DS
authors.lastname: Stribling
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shearman
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001667:Binding, Competitive / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D043884:Receptor, Cannabinoid, CB1