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Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy
With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L-amino acids (6a–o) were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 μmol/kg 6a–o exhibited excellen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410827/ https://www.ncbi.nlm.nih.gov/pubmed/25960636 http://dx.doi.org/10.2147/DDDT.S76218 |
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author | Jiang, Xueyun Wang, Yuji Zhu, Haimei Wang, Yaonan Zhao, Ming Zhao, Shurui Wu, Jianhui Li, Shan Peng, Shiqi |
author_facet | Jiang, Xueyun Wang, Yuji Zhu, Haimei Wang, Yaonan Zhao, Ming Zhao, Shurui Wu, Jianhui Li, Shan Peng, Shiqi |
author_sort | Jiang, Xueyun |
collection | PubMed |
description | With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L-amino acids (6a–o) were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 μmol/kg 6a–o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 μmol/kg. The correlation of the three-dimensional quantitative structure–activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain. |
format | Online Article Text |
id | pubmed-4410827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44108272015-05-08 Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy Jiang, Xueyun Wang, Yuji Zhu, Haimei Wang, Yaonan Zhao, Ming Zhao, Shurui Wu, Jianhui Li, Shan Peng, Shiqi Drug Des Devel Ther Original Research With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L-amino acids (6a–o) were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 μmol/kg 6a–o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 μmol/kg. The correlation of the three-dimensional quantitative structure–activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain. Dove Medical Press 2015-04-22 /pmc/articles/PMC4410827/ /pubmed/25960636 http://dx.doi.org/10.2147/DDDT.S76218 Text en © 2015 Jiang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Jiang, Xueyun Wang, Yuji Zhu, Haimei Wang, Yaonan Zhao, Ming Zhao, Shurui Wu, Jianhui Li, Shan Peng, Shiqi Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title | Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title_full | Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title_fullStr | Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title_full_unstemmed | Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title_short | Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy |
title_sort | modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3d-qsar for improving inflammatory pain therapy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410827/ https://www.ncbi.nlm.nih.gov/pubmed/25960636 http://dx.doi.org/10.2147/DDDT.S76218 |
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