Peripherally-restricted cannabinoid receptor 1 (CB1) selective antagonists have the potential to inhibit food intake while also escaping centrally-mediated neuropsychiatric side effects. AM6545 is a novel CB1 selective neutral antagonist with low CNS penetration, exhibiting Ki values of 1.7 and 523 nM for CB1 and CB2 receptors, respectively. It reduces food intake and food-reinforced behavior, such as time spent feeding, in a dose-dependent manner, resulting in decreased body weight. AM6545 produces improvements in glucose homeostasis, fatty liver, and plasma lipid profiles in mice with diet-induced obesity. It does not affect behavior responses that are associated with activation of CB1 receptors in the brain.
![5-(4-[4-cyanobut-1-ynyl]phenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(1,1-dioxo-thiomorpholino)-1H-pyrazole-3-carboxamide](https://www.chemicalbook.com/CAS/20180703/GIF/1245626-05-4.gif)
