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Three-dimensional pharmacophore screening for fentanyl derivatives☆

Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to id...

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Detalles Bibliográficos
Autores principales: Liu, Ming, Sun, Zhiguo, Hu, Wenxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308790/
https://www.ncbi.nlm.nih.gov/pubmed/25657673
http://dx.doi.org/10.3969/j.issn.1673-5374.2012.18.006
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author Liu, Ming
Sun, Zhiguo
Hu, Wenxiang
author_facet Liu, Ming
Sun, Zhiguo
Hu, Wenxiang
author_sort Liu, Ming
collection PubMed
description Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.
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spelling pubmed-43087902015-02-05 Three-dimensional pharmacophore screening for fentanyl derivatives☆ Liu, Ming Sun, Zhiguo Hu, Wenxiang Neural Regen Res Techniques and Method: Emerging Technology in Neural Regeneration Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures. Medknow Publications & Media Pvt Ltd 2012-06-25 /pmc/articles/PMC4308790/ /pubmed/25657673 http://dx.doi.org/10.3969/j.issn.1673-5374.2012.18.006 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Techniques and Method: Emerging Technology in Neural Regeneration
Liu, Ming
Sun, Zhiguo
Hu, Wenxiang
Three-dimensional pharmacophore screening for fentanyl derivatives☆
title Three-dimensional pharmacophore screening for fentanyl derivatives☆
title_full Three-dimensional pharmacophore screening for fentanyl derivatives☆
title_fullStr Three-dimensional pharmacophore screening for fentanyl derivatives☆
title_full_unstemmed Three-dimensional pharmacophore screening for fentanyl derivatives☆
title_short Three-dimensional pharmacophore screening for fentanyl derivatives☆
title_sort three-dimensional pharmacophore screening for fentanyl derivatives☆
topic Techniques and Method: Emerging Technology in Neural Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308790/
https://www.ncbi.nlm.nih.gov/pubmed/25657673
http://dx.doi.org/10.3969/j.issn.1673-5374.2012.18.006
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