Design And Synthesis Of Dual-Affinity Molecular Probes Targeting The Opioid Receptors

Abstract

There continues to be a critical demand for the design and development of novel opioid receptor ligands that can both function as therapeutic analgesics (i.e. tolerable ADMET properties) and address the problem of drug addiction associated with classic opioid receptor ligands. However, the vast majority of pharmacological research continues to revisit the classic opioid scaffolds (e.g. morphine) [1]. The first step in addressing these issues is the design and development of new molecular probes capable of functioning as essential research tools. We utilize a unique natural product pharmacophore: salvinorin A. This neoclerodane diterpenoid, isolated from Salvia divinorum, is a potent KOR subtype-selective ligand that binds in a manner distinct from the classic opioid ligands [2].