Functionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor.

ABSTRACT: Peripherally restricted CB1 receptor antagonists may be useful in treating metabolic syndrome, diabetes, liver diseases, and gastrointestinal disorders. Clinical development of the centrally acting CB1 inverse agonist otenabant (1) was halted due to its potential of producing adverse effects. SAR studies of 1 are reported herein with the objective of producing peripherally restricted analogues. Crystal structures of hCB1 and docking studies with 1 indicate that the piperidine group could be functionalized at the 4-position to access a binding pocket that can accommodate both polar and nonpolar groups. The piperidine is studied as a linker, functionalized with alkyl, heteroalkyl, aryl, and heteroaryl groups using a urea connector. Orally bioavailable and peripherally se

SUBMITTER: Amato G 

PROVIDER: S-EPMC7656562 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature