Studies toward the Pharmacophore of Salvinorin A, a Potent κ Opioid Receptor Agonist

Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective κ opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to μ or δ opioid receptors.