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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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Detalles Bibliográficos
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
Descripción
Sumario: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.