1. Tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists
- Author
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Cailin Chen, Yin Liang, Mingde Xia, Bin Zhu, Cuifen Hou, Matthews Jay M, Shawn Black, Yuting Tang, and Mark J. Macielag
- Subjects
0301 basic medicine ,Male ,Cannabinoid receptor ,Drug Inverse Agonism ,Stereochemistry ,Pyridines ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,Biochemistry ,Polar surface area ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Receptor, Cannabinoid, CB1 ,Drug Discovery ,Pyridine ,medicine ,Inverse agonist ,Animals ,Humans ,Tissue Distribution ,Tissue distribution ,Obesity ,Molecular Biology ,Cannabinoid Receptor Antagonists ,Chemistry ,Organic Chemistry ,Brain ,Mice, Inbred C57BL ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Cannabinoid receptor antagonist ,Pyrazoles ,Cannabinoid - Abstract
Peripherally restricted CB1 receptor inverse agonists hold potential as useful therapeutics to treat obesity and related metabolic diseases without causing undesired CNS-mediated adverse effects. We identified a series of tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and highly peripherally selective CB1 receptor inverse agonists. This discovery was achieved by introducing polar functional groups into the molecule, which increase the topological polar surface area and reduce its brain-penetrating ability.
- Published
- 2016