Modifying tetramethyl-nitrophenyl-imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy

利用氨基酸修饰四甲基硝基苯基咪唑啉:设计、合成及三维定量构效关系研究,以改善炎症性疼痛治疗

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Abstract

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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