Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.
Bioorganic & medicinal chemistry letters May 15, 2013 Prabhakar R Polepally, Kate White, Eyal Vardy et al. 24 citations
Salvinorin A, the active ingredient in the hallucinogenic plant Salvia divinorum, is nature's most potent hallucinogen and selectively activates the κ-opioid receptor. To explore how these compounds bind to specific receptors, researchers synthesized a series of dicarboxylic ester derivatives of salvinorin A and tested their binding affinity at κ-, δ-, and μ-opioid receptors. Most of the new compounds showed high affinity for the κ-opioid receptor. The methyl malonyl derivative 4 had the strongest binding, with a Ki of 2 nM, while analogues 5, 7, and 14 also exhibited significant affinity, with Ki values of 21, 36, and 39 nM respectively. These findings provide insights into brain chemistry and ligand-receptor interactions.