• Journal Article

Identification of the first trans-(3R,4R)-dimethyl-4-(3- hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity

Citation

Thomas, J., Atkinson, R., Rothman, R. B., Fix, S., Mascarella, S., Vinson, N., ... Carroll, F. (2001). Identification of the first trans-(3R,4R)-dimethyl-4-(3- hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity. Journal of Medicinal Chemistry, 44(17), 2687-2690. DOI: 10.1021/jm015521r

Abstract

A structurally novel opioid kappa receptor selective
ligand has been identified. This compound, (3R)-7-hydroxy-
N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]
methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide
(JDTic, 10) demonstrated high affinity for the
kappa receptor in the binding assay (kappa Ki ) 0.3 nM) and highly
potent and selective kappa antagonism in the [35S]GTP-ç-S assay
using cloned opioid receptors (kappa Ki ) 0.006 nM, u/kappa ratio )
570, ä/kappa ratio > 16600).