Functionalized 6-(piperidin-1-yl)-8,9-diphenyl purines as inverse agonists of the CB1 receptor - SAR efforts towards selectivity and peripheralization.

ABSTRACT: Antagonists of type 1 cannabinoid receptors (CB1) may be useful in treating diabetes, hepatic disorders, and fibrosis. Otenabant (1) is a potent and selective CB1 inverse agonist that was under investigation as an anti-obesity agent, but its development was halted once adverse effects associated with another marketed inverse agonist rimonabant (2) became known. Non-tissue selective antagonists of CB1 that have high levels of brain penetration produce adverse effects in a small subset of patients including anxiety, depression and suicidal ideation. Currently, efforts are underway to produce compounds that have limited brain penetration. In this report, novel analogs of 1 are explored to develop and test strategies for peripheralization. The piperidine of 1 is studied as a linker, which is f

SUBMITTER: Amato G 

PROVIDER: S-EPMC6660994 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature