N-Alkyl-octahydroisoquinolin-1-one-8-carboxamides: a Novel Class of Selective, Nonbasic, Nitrogen-Containing κ-Opioid Receptor Ligands.
Herein we report that N-alkyl-octahydroisoquinolin-1-one-8-carboxamides are a novel class of readily-synthesized, selective ϰ-opioid receptor (KOR) ligands. A striking feature of this class of compounds is the absence of any basic nitrogen atoms. Many of these compounds have demonstrated exclusive affinity for the KOR over not only the δ-opioid receptor (DOR) and the μ-opioid receptor (MOR), but 38 other GPCR targets as well. The general binding affinity of this class of compounds for the KOR combined with a streamlined route for analog synthesis provide strong motivation for pursuing this interesting new scaffold as a basis toward new probes targeting the KOR.
Frankowski
Kevin J
KJ
Department of Medicinal Chemistry, University of Kansas, 2121 Simons Drive, Lawrence, Kansas 66047.
Ghosh
Partha
P
Setola
Vincent
V
Tran
Thuy B
TB
Roth
Bryan L
BL
Aubé
Jeffrey
J