1. Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists
- Author
-
Peter J. Connolly, Cuifen Hou, Mark J. Macielag, Shawn Black, Mcnally James J, Mingde Xia, Matthews Jay M, Yuting Tang, Bin Zhu, Yin Liang, and Cailin Chen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Indazoles ,Cannabinoid receptor ,Drug Inverse Agonism ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,Biochemistry ,Receptor, Cannabinoid, CB2 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Receptor, Cannabinoid, CB1 ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Inverse agonist ,Distribution (pharmacology) ,Receptor ,Molecular Biology ,Beneficial effects ,Chemistry ,Organic Chemistry ,Peripheral ,030104 developmental biology ,Endocrinology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Cannabinoid ,Efficacy Study - 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.
- Published
- 2016
- Full Text
- View/download PDF