Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a Novel, Acyclic Cannabinoid
文摘
The discovery of novel acyclic amide cannabinoid-1 receptorinverse agonists is described. They are potent, selective, orallybioavailable, and active in rodent models of food intake and body weightreduction. A major focus of the optimization process was to increasein vivo efficacy and to reduce the potential for formation of reactivemetabolites. These efforts led to the identification of compound 48 fordevelopment as a clinical candidate for the treatment of obesity.