4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective δ-opioid agonists

A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for δ-, μ-, and κ-opioid receptors, as well as the functional activity in the [35S]GTPγS assay are reported. The most potent and selective δ-opioid agonist 18a exhibited a Ki of 18 nM, and was >258-fold and 28-fold selective over μ- and κ-receptors, respectively; the compound is a full agonist with an EC50 value of 14 nM.

Graphical abstractA new chemical class of selective δ-opioid agonists based on the 4-phenyl-4-[1H-imidazol-2-yl]-piperidine scaffold is reported. A highly selective δ agonist (18a, EC50 = 14 nM) was identified.Figure optionsDownload full-size imageDownload as PowerPoint slide