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 and the μ-opioid receptor but also 38 other G protein-coupled receptor targets. The general binding affinity of this class of compounds for the KOR combined with a streamlined route for analogue synthesis provide strong motivation for pursuing this interesting new scaffold as a basis toward new probes targeting the KOR
