Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists

[Image: see text] Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1–4 on ligand–MOR interaction, signaling, and antinociception. While 6-desoxo...

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Autores principales: Dumitrascuta, Maria, Ben Haddou, Tanila, Guerrieri, Elena, Noha, Stefan M., Schläfer, Lea, Schmidhammer, Helmut, Spetea, Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706069/
https://www.ncbi.nlm.nih.gov/pubmed/29053268
http://dx.doi.org/10.1021/acs.jmedchem.7b01363
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author Dumitrascuta, Maria
Ben Haddou, Tanila
Guerrieri, Elena
Noha, Stefan M.
Schläfer, Lea
Schmidhammer, Helmut
Spetea, Mariana
author_facet Dumitrascuta, Maria
Ben Haddou, Tanila
Guerrieri, Elena
Noha, Stefan M.
Schläfer, Lea
Schmidhammer, Helmut
Spetea, Mariana
author_sort Dumitrascuta, Maria
collection PubMed
description [Image: see text] Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1–4 on ligand–MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compared with its analogue 3.
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spelling pubmed-57060692017-11-30 Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists Dumitrascuta, Maria Ben Haddou, Tanila Guerrieri, Elena Noha, Stefan M. Schläfer, Lea Schmidhammer, Helmut Spetea, Mariana J Med Chem [Image: see text] Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1–4 on ligand–MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compared with its analogue 3. American Chemical Society 2017-10-20 2017-11-22 /pmc/articles/PMC5706069/ /pubmed/29053268 http://dx.doi.org/10.1021/acs.jmedchem.7b01363 Text en Copyright © 2017 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Dumitrascuta, Maria
Ben Haddou, Tanila
Guerrieri, Elena
Noha, Stefan M.
Schläfer, Lea
Schmidhammer, Helmut
Spetea, Mariana
Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title_full Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title_fullStr Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title_full_unstemmed Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title_short Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists
title_sort synthesis, pharmacology, and molecular docking studies on 6-desoxo-n-methylmorphinans as potent μ-opioid receptor agonists
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706069/
https://www.ncbi.nlm.nih.gov/pubmed/29053268
http://dx.doi.org/10.1021/acs.jmedchem.7b01363
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