Literature DB >> 27148755

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

Aubrie A Harland1, Aaron M Bender1, Nicholas W Griggs2, Chao Gao2, Jessica P Anand2, Irina D Pogozheva3, John R Traynor2, Emily M Jutkiewicz2, Henry I Mosberg1,3.   

Abstract

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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Year:  2016        PMID： 27148755      PMCID： PMC4885601          DOI： 10.1021/acs.jmedchem.6b00308

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  31 in total

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2.  Complex of an active mu-opioid receptor with a cyclic peptide agonist modeled from experimental constraints.

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3.  In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu-agonist/delta-antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence.

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Authors:  M J Hepburn; P J Little; J Gingras; C M Kuhn
Journal:  J Pharmacol Exp Ther       Date:  1997-06       Impact factor: 4.030

5.  Differential binding properties of oripavines at cloned mu- and delta-opioid receptors.

Authors:  K O Lee; H Akil; J H Woods; J R Traynor
Journal:  Eur J Pharmacol       Date:  1999-08-13       Impact factor: 4.432

6.  BU74, a complex oripavine derivative with potent kappa opioid receptor agonism and delayed opioid antagonism.

Authors:  Stephen M Husbands; Claire L Neilan; Jillian Broadbear; Peter Grundt; Simon Breeden; Mario D Aceto; James H Woods; John W Lewis; John R Traynor
Journal:  Eur J Pharmacol       Date:  2005-02-21       Impact factor: 4.432

7.  Key residues defining the mu-opioid receptor binding pocket: a site-directed mutagenesis study.

Authors:  A Mansour; L P Taylor; J L Fine; R C Thompson; M T Hoversten; H I Mosberg; S J Watson; H Akil
Journal:  J Neurochem       Date:  1997-01       Impact factor: 5.372

8.  Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells.

Authors:  J R Traynor; S R Nahorski
Journal:  Mol Pharmacol       Date:  1995-04       Impact factor: 4.436

9.  Attenuation of morphine tolerance and dependence with the highly selective delta-opioid receptor antagonist TIPP[psi].

Authors:  M E Fundytus; P W Schiller; M Shapiro; G Weltrowska; T J Coderre
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10.  Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities.

Authors:  Aubrie A Harland; Larisa Yeomans; Nicholas W Griggs; Jessica P Anand; Irina D Pogozheva; Emily M Jutkiewicz; John R Traynor; Henry I Mosberg
Journal:  J Med Chem       Date:  2015-11-13       Impact factor: 7.446
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  10 in total

1.  Aromatic-Amine Pendants Produce Highly Potent and Efficacious Mixed Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Peptidomimetics with Enhanced Metabolic Stability.

Authors:  Sean Henry; Jessica P Anand; Jack J Twarozynski; Ashley C Brinkel; Irina D Pogozheva; Bryan F Sears; Emily M Jutkiewicz; John R Traynor; Henry I Mosberg
Journal:  J Med Chem       Date:  2020-02-10       Impact factor: 7.446

2.  Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic μ-Opioid Receptor (MOR) Agonist/δ-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability.

Authors:  Sean P Henry; Thomas J Fernandez; Jessica P Anand; Nicholas W Griggs; John R Traynor; Henry I Mosberg
Journal:  J Med Chem       Date:  2019-04-12       Impact factor: 7.446

3.  A Novel Mu-Delta Opioid Agonist Demonstrates Enhanced Efficacy With Reduced Tolerance and Dependence in Mouse Neuropathic Pain Models.

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4.  Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show in Vitro Kappa and Mu Opioid Receptor Agonism.

Authors:  Deanna Montgomery; Jessica P Anand; Nicholas W Griggs; Thomas J Fernandez; Joshua G Hartman; Ashley A Sánchez-Santiago; Irina D Pogozheva; John R Traynor; Henry I Mosberg
Journal:  ACS Chem Neurosci       Date:  2019-07-01       Impact factor: 4.418

5.  Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands.

Authors:  Jason R Healy; Padmavani Bezawada; Nicholas W Griggs; Andrea L Devereaux; Rae R Matsumoto; John R Traynor; Andrew Coop; Christopher W Cunningham
Journal:  Bioorg Med Chem Lett       Date:  2016-11-22       Impact factor: 2.823

6.  Dual Pharmacophores Explored via Structure-Activity Relationship (SAR) Matrix: Insights into Potent, Bifunctional Opioid Ligand Design.

Authors:  Anthony F Nastase; Jessica P Anand; Aaron M Bender; Deanna Montgomery; Nicholas W Griggs; Thomas J Fernandez; Emily M Jutkiewicz; John R Traynor; Henry I Mosberg
Journal:  J Med Chem       Date:  2019-04-09       Impact factor: 7.446

Review 7.  Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain.

Authors:  Keith M Olson; Wei Lei; Attila Keresztes; Justin LaVigne; John M Streicher
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8.  Placement of Hydroxy Moiety on Pendant of Peptidomimetic Scaffold Modulates Mu and Kappa Opioid Receptor Efficacy.

Authors:  Aubrie A Harland; Irina D Pogozheva; Nicholas W Griggs; Tyler J Trask; John R Traynor; Henry I Mosberg
Journal:  ACS Chem Neurosci       Date:  2017-08-25       Impact factor: 4.418

9.  Structure-Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics.

Authors:  Deanna Montgomery; Jessica P Anand; Mason A Baber; Jack J Twarozynski; Joshua G Hartman; Lennon J Delong; John R Traynor; Henry I Mosberg
Journal:  Molecules       Date:  2019-11-26       Impact factor: 4.411

10.  Toward a Universal μ-Agonist Template for Template-Based Alignment Modeling of Opioid Ligands.

Authors:  Zhijun Wu; Victor J Hruby
Journal:  ACS Omega       Date:  2019-10-09
  10 in total

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