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Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy ?-Opioid Receptor (MOR)/?-Opioid Receptor (DOR) Ligands.

ABSTRACT: N-Acetylation of the tetrahydroquinoline (THQ) core of a series of ?-opioid receptor (MOR) agonist/?-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.

SUBMITTER: Harland AA

PROVIDER: S-EPMC4885601 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Harland Aubrie A AA Bender Aaron M AM Griggs Nicholas W NW Gao Chao C Anand Jessica P JP Pogozheva Irina D ID Traynor John R JR Jutkiewicz Emily M EM Mosberg Henry I HI

Journal of medicinal chemistry 20160516 10

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 ...[more]

PMID: 27148755

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