替泊沙林的新合成方法及其镇痛活性的研究

Novel synthetic method and analgesic activity of tepoxalin

替泊沙林(tepoxalin)是一种有效的花生四烯酸级联反应的环氧合酶和脂氧合酶代谢抑制剂,具有抗炎、治疗多种疼痛(手术后、关节等)等多种药物活性。本文采用新的合成试剂,首次以离子液体为反应溶剂,找到了一种合成替泊沙林的新方法。利用小鼠醋酸扭体法对替泊沙林的镇痛活性进行了研究。方差分析结果表明:替泊沙林给药组和CMC对照组间扭体反应潜伏期及1h内小鼠的扭体次数均有显著性的差异(P<0.05);并且替泊沙林可剂量依赖性地延长注射冰醋酸后的扭体反应潜伏期并减少1h内小鼠的扭体次数,替泊沙林对扭体反应的潜伏期及1h内扭体次数的抑制作用和双氯酚酸钠(diclofenac sodium)无显著性差异。

Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain （ postoperation, arthritis et al） agent. The new method about the use of novel synthesis reagents and the first using ionic liquid as reactive solvent to synthesize tepoxalin were presented in this paper. The ionic liquid can be easily recycled and reused for several runs efficiently. The analgesic activity of tepoxalin was detected by acetic acid test on mice. The analysis of variance showed that oral administration of tepoxalin could significantly inhibit the number of writhing response within 1 hour and prolong the latent time in a dose dependent manner as compared with CMC control group （P 〈 0.05）. At the same time, tepoxalin had the same analgesic activity as diclofenac sodium.