Pyrimidinyl Biphenylureas: Identification of New Lead Compounds as Allosteric Modulators of the Cannabinoid Receptor CB₁.

ABSTRACT: The allosteric modulator 1-(4-chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 2) bound the cannabinoid receptor 1 (CB₁) and antagonized G protein coupling. This compound demonstrated potent anorectic effects similar to the CB₁ antagonist rimonabant that once was marketed for the treatment of obesity, suggesting a new chemical entity for the discovery of antiobesity drugs. To increase structural diversity of this class of CB₁ ligands, we designed and synthesized two classes of novel analogues, in which the pyridine ring of 2 was replaced by a pyrimidine ring. These positively modulate the binding of the CB₁ orthosteric agonist CP55,940 while exhibiting an antagonism of G-protein coupling activity. Interestingly, compoun

SUBMITTER: Khurana L 

PROVIDER: S-EPMC5724760 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature