Discovery of N-[(4R)-6-(4-Chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a Novel Cannabinoid-1 Receptor (CB1R) Inverse Agonist for the Treatment of Obesity - Yan, Lin; Huo, Pei; Debenham, John S; Madsen-Duggan, Christina B; Lao, Julie; Chen, Richard Z; Xiao, Jing Chen; Shen, Chun-Pyn; Stribling, D. Sloan; Shearman, Lauren P; Strack, Alison M; Tsou, Nancy; et al. (Journal of medicinal chemistry, 2010)
Keywords: Animals; Anti-Obesity Agents - chemical synthesis; Anti-Obesity Agents - pharmacokinetics; Anti-Obesity Agents - pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Binding, Competitive; Body Weight - drug effects; Cell Line; Cricetinae; Cricetulus; Crystallography, X-Ray; Dogs; Drug Inverse Agonism; Eating - drug effects; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors; Glucuronides - metabolism; Haplorhini; Hepatocytes - metabolism; Humans; Mice; Mice, Knockout; Models, Molecular; Molecular Conformation; Pyrans - chemical synthesis; Pyrans - pharmacokinetics; Pyrans - pharmacology; Pyridines - chemical synthesis; Pyridines - pharmacokinetics; Pyridines - pharmacology; Rats; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - genetics; Stereoisomerism; Structure-Activity Relationship