Rimonabant-Based Compounds Bearing Hydrophobic Amino Acid Derivatives as Cannabinoid Receptor Subtype 1 Ligands.

ABSTRACT: In this study, 1H-pyrazole-3-carboxylic acids related to the cannabinoid type 1 (CB1) receptor antagonist rimonabant were amidated with valine or tert-leucine, and the resulting acids were further diversified as methyl esters, amides, and N-methyl amides. In vitro receptor binding and functional assays demonstrated a wide series of activities related to the CB1 receptors (CB1Rs). Compound 34 showed a high CB1R binding affinity (K _i = 6.9 nM) and agonist activity (EC₅₀ = 46 nM; E _max = 135%). Radioligand binding and [³⁵S]GTPγS binding assays also demonstrated its selectivity and specificity to CB1Rs. Moreover, in vivo experiments revealed that 34 was slightly more effective than the CB

SUBMITTER: Dvoracsko S 

PROVIDER: S-EPMC10108392 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature