4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists.
Bioorganic & medicinal chemistry letters 2006 Jan 1; 16(1):146-9
Trabanco A AA, Pullan S S, Alonso J JM, Alvarez R RM, Andrés J JI, Boeckx I I, Fernández J J, Gómez A A, Iturrino L L, Janssens F FE, Leenaerts J JE, De Lucas A AI, Matesanz E E, Meert T T, Steckler T T
Division of Psychiatry, Research and Early Development Europe, Johnson and Johnson Pharmaceutical Research and Development, Jarama 75, 47007 Toledo, Spain. atrabanc@prdes.jnj.com
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 delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [(35)S]GTPgammaS assay are reported. The most potent and selective delta-opioid agonist 18a exhibited a K(i) of 18 nM, and was >258-fold and 28-fold selective over mu- and kappa-receptors, respectively; the compound is a full agonist with an EC(50) value of 14 nM.