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

[Image: see text] 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 in...

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Autores principales: Harland, Aubrie A., Bender, Aaron M., Griggs, Nicholas W., Gao, Chao, Anand, Jessica P., Pogozheva, Irina D., Traynor, John R., Jutkiewicz, Emily M., Mosberg, Henry I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885601/
https://www.ncbi.nlm.nih.gov/pubmed/27148755
http://dx.doi.org/10.1021/acs.jmedchem.6b00308
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author Harland, Aubrie A.
Bender, Aaron M.
Griggs, Nicholas W.
Gao, Chao
Anand, Jessica P.
Pogozheva, Irina D.
Traynor, John R.
Jutkiewicz, Emily M.
Mosberg, Henry I.
author_facet Harland, Aubrie A.
Bender, Aaron M.
Griggs, Nicholas W.
Gao, Chao
Anand, Jessica P.
Pogozheva, Irina D.
Traynor, John R.
Jutkiewicz, Emily M.
Mosberg, Henry I.
author_sort Harland, Aubrie A.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-48856012017-05-05 Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands Harland, Aubrie A. Bender, Aaron M. Griggs, Nicholas W. Gao, Chao Anand, Jessica P. Pogozheva, Irina D. Traynor, John R. Jutkiewicz, Emily M. Mosberg, Henry I. J Med Chem [Image: see text] 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. American Chemical Society 2016-05-05 2016-05-26 /pmc/articles/PMC4885601/ /pubmed/27148755 http://dx.doi.org/10.1021/acs.jmedchem.6b00308 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Harland, Aubrie A.
Bender, Aaron M.
Griggs, Nicholas W.
Gao, Chao
Anand, Jessica P.
Pogozheva, Irina D.
Traynor, John R.
Jutkiewicz, Emily M.
Mosberg, Henry I.
Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title_full Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title_fullStr Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title_full_unstemmed Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title_short Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands
title_sort effects of n-substitutions on the tetrahydroquinoline (thq) core of mixed-efficacy μ-opioid receptor (mor)/δ-opioid receptor (dor) ligands
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885601/
https://www.ncbi.nlm.nih.gov/pubmed/27148755
http://dx.doi.org/10.1021/acs.jmedchem.6b00308
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