Modifying tetramethyl-nitrophenyl-imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy.
Modifying tetramethyl-nitrophenyl-imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy.
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DOI：
10.2147/dddt.s76218
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Peng S
中科院分区：
文献类型：
--
作者：
Jiang X;Wang Y;Zhu H;Wang Y;Zhao M;Zhao S;Wu J;Li S;Peng S
通过药效团分析和对接研究，设计、合成了15种新型1-（4,4,5,5-四甲基-2-（3-硝基苯基）-4,5-二氢咪唑-1-基）-氧乙酰基- l氨基酸（6a-o），并进行了分析。在甩尾和二甲苯诱导的耳部水肿模型中，10 μmol/kg 6a-o具有良好的口服抗炎和镇痛活性。对其代表性的6f进行剂量依赖性测定，有效剂量为3.3 μmol/kg。将三维定量构效关系与对接分析相结合，为合理设计治疗炎症性疼痛的药物提供依据。
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.