• 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

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).

Citation

Thomas, J., Atkinson, R., Rothman, RB., 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. https://doi.org/10.1021/jm015521r

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