Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
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- 作者：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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：May 26, 2016
- 年：2016
- 卷：59
- 期：10
- 页码：4985-4998
- 全文大小：605K
- 年卷期：0
- ISSN：1520-4804
文摘
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.