Exceptionally Potent Chiral Anandamide Analogs.

ABSTRACT: We recently reported an innovative design approach that allowed us to obtain potent endocannabinoids with enhanced metabolic stability. Our design is characterized by the incorporation of chiral centers within the endocannabinoid prototypes N-arachidonoylethanolamide and 2-arachidonoylglycerol. Work on N-arachidonoylethanolamide led to the identification of the first-generation lead analog (R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AMG315). Here, we synthesized a series of tail-modified AMG315 analogs to further optimize this novel chemotype for cannabinoid receptor binding affinity and potency. Our advanced molecule, namely, 20,20,20-trifluoro-(R)-N-(1-methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AM12814, <

SUBMITTER: Georgiadis MO 

PROVIDER: S-EPMC12915296 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature