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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...

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Autores principales: Jiang, Xueyun, Wang, Yuji, Zhu, Haimei, Wang, Yaonan, Zhao, Ming, Zhao, Shurui, Wu, Jianhui, Li, Shan, Peng, Shiqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
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.
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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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