4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists.
Trabanco AA,
Pullan S,
Alonso JM,
Alvarez RM,
Andrés JI,
Boeckx I,
Fernández J,
Gómez A,
Iturrino L,
Janssens FE,
Leenaerts JE,
De Lucas AI,
Matesanz E,
Meert T,
Steckler 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.
PMID: 16236510 [PubMed - indexed for MEDLINE]