Open AccessEffects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
Author(s) -
Aubrie A. Harland,
Aaron M. Bender,
Nicholas W. Griggs,
Chao Gao,
Jessica P. Anand,
Irina D. Pogozheva,
John R. Traynor,
Emily M. Jutkiewicz,
Henry I. Mosberg
Publication year - 2016
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.6b00308
Subject(s) - chemistry , opioid receptor , steric effects , opioid , stereochemistry , receptor , agonist , antagonist , affinities , ligand (biochemistry) , pharmacology , biochemistry , medicine
N-Acetylation of the tetrahydroquinoline (THQ) core of a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands increases DOR affinity, resulting in ligands with balanced MOR and DOR affinities. We report a series of N-substituted THQ analogues that incorporate various carbonyl-containing moieties to maintain DOR affinity and define the steric and electronic requirements of the binding pocket across the opioid receptors. 4h produced in vivo antinociception (ip) for 1 h at 10 mg/kg.