Effects of <i>N</i>‑Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ‑Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands

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.