Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists

Abstract

A series of potent and receptor-selective cannabinoid-1 (CB1) receptor inverse agonists has been discovered. Peripheral selectivity of the compounds was assessed by a mouse tissue distribution study, in which the concentrations of a test compound in both plasma and brain were measured. A number of peripherally selective compounds have been identified through this process. Compound 2p was further evaluated in a 3-week efficacy study in the diet-induced obesity (DIO) mouse model. Beneficial effects on plasma glucose were observed from the compound-treated mice.

Keywords: CB1 receptor; Cannabinoid receptor; Inverse agonist; Peripheral selectivity; Peripherally restricted.