Blocking Alcoholic Steatosis in Mice with a Peripherally Restricted Purine Antagonist of the Type 1 Cannabinoid Receptor.

ABSTRACT: Type 1 cannabinoid receptor (CB1) antagonists have demonstrated promise for the treatment of obesity, liver disease, metabolic syndrome, and dyslipidemias. However, the inhibition of CB1 receptors in the central nervous system can produce adverse effects, including depression, anxiety, and suicidal ideation. Efforts are now underway to produce peripherally restricted CB1 antagonists to circumvent CNS-associated undesirable effects. In this study, a series of analogues were explored in which the 4-aminopiperidine group of compound 2 was replaced with aryl- and heteroaryl-substituted piperazine groups both with and without a spacer. This resulted in mildly basic, potent antagonists of human CB1 (hCB1). The 2-chlorobenzyl piperazine, 25, was found to be potent ( K_i = 8 nM); to be >

SUBMITTER: Amato GS 

PROVIDER: S-EPMC7607848 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature