Synthesis and activity of 4,5-diarylimidazoles as human CB1 receptor inverse agonists.
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.
Plummer
Christopher W
CW
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. christopher_plummer@merck.com
Finke
Paul E
PE
Mills
Sander G
SG
Wang
Junying
J
Tong
Xinchun
X
Doss
George A
GA
Fong
Tung M
TM
Lao
Julie Z
JZ
Schaeffer
Marie-Therese
MT
Chen
Jing
J
Shen
Chun-Pyn
CP
Stribling
D Sloan
DS
Shearman
Lauren P
LP
Strack
Alison M
AM
Van der Ploeg
Lex H T
LH
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
D007093:Imidazoles; D043884:Receptor, Cannabinoid, CB1