Jiang Xueyun, Wang Yuji, Zhu Haimei, Wang Yaonan, Zhao Ming, Zhao Shurui, Wu Jianhui, Li Shan, Peng Shiqi
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China ; Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Drug Des Devel Ther. 2015 Apr 22;9:2329-42. doi: 10.2147/DDDT.S76218. eCollection 2015.
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.
借助药效团分析和对接研究，设计、合成并测定了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)。在甩尾和二甲苯诱导的耳水肿模型上，10 μmol/kg的6a-o表现出优异的口服抗炎和镇痛活性。其代表性化合物6f的剂量依赖性试验表明有效剂量应为3.3 μmol/kg。三维定量构效关系与对接分析的相关性为合理设计治疗炎性疼痛的药物提供了依据。
