jm015521r_si_001.pdf (103.41 kB)
Download file

Identification of the First trans-(3R,4R)- Dimethyl-4-(3-hydroxyphenyl)piperidine Derivative To Possess Highly Potent and Selective Opioid κ Receptor Antagonist Activity

Download (103.41 kB)
journal contribution
posted on 14.07.2001, 00:00 by James B. Thomas, Robert N. Atkinson, Richard B. Rothman, Scott E. Fix, S. Wayne Mascarella, N. Ariane Vinson, Heng Xu, Christina M. Dersch, Y. -F. Lu, Buddy E. Cantrell, Dennis M. Zimmerman, F. Ivy Carroll
A structurally novel opioid κ 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 κ receptor in the binding assay (κ Ki = 0.3 nM) and highly potent and selective κ antagonism in the [35S]GTP-γ-S assay using cloned opioid receptors (κ Ki = 0.006 nM, μ/κ ratio = 570, δ/κ ratio > 16600).