Structure-Affinity Relationships and Structure-Kinetic Relationships of 1,2-Diarylimidazol-4-carboxamide Derivatives as Human Cannabinoid 1 Receptor Antagonists.

ABSTRACT: We report on the synthesis and biological evaluation of a series of 1,2-diarylimidazol-4-carboxamide derivatives developed as CB₁ receptor antagonists. These were evaluated in a radioligand displacement binding assay, a [³⁵S]GTPγS binding assay, and in a competition association assay that enables the relatively fast kinetic screening of multiple compounds. The compounds show high affinities and a diverse range of kinetic profiles at the CB₁ receptor and their structure-kinetic relationships (SKRs) were established. Using the recently resolved hCB₁ receptor crystal structures, we also performed a modeling study that sheds light on the crucial interactions for both the affinity and dissociation kinetics of this family of ligands. We provide evidenc

SUBMITTER: Xia L 

PROVIDER: S-EPMC5734604 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature