四氢喹啉类化合物的合成及镇痛活性的研究

【作者】 刘永福；

【导师】 宋宏锐；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2005， 硕士

【摘要】 本论文是关于4-(1H-吡咯-2-基)-1，2，3，4-四氢喹啉类化合物的合成及镇痛活性与构效关系的研究。 四氢吡咯里嗪并[2，1-c]喹啉类化合物是在对芳氨甲基吡里酮衍生物Z-47的结构改造过程中发现的具有较强镇痛作用的吡里酮衍生物。本论文是在对其结构研究的基础上，对四氢吡咯里嗪并[2，1-c]喹啉类化合物的结构做进一步的简化，以强化其镇痛活性为目的，并结合阿片类镇痛药吗啡衍生物和哌替啶的构效关系，设计合成了二十个未见文献报道的4-(1H-吡咯-2-基)-1，2，3，4-四氢喹啉类化合物，其结构经~1H-NMR，MS确定。 以醋酸致小鼠扭体法对所合成的目标化合物进行镇痛活性试验。结果表明，以200mg／kg剂量小鼠灌胃给药，多数化合物显示出一定程度的镇痛作用，其中以FLY-1、FLY-6、FLY-12、FLY-14、FLY-15的镇痛作用较强，值得深入研究。初步总结了该类化合物的构效关系规律。更多还原

【Abstract】 The study on synthesis and structure-activity relationships (SAR) of 4-(1H-pyrrol-2-yl)-tetrahydroquinoline derivatives is reported in this paper.Tetrahydropyrrolizino[2, 1-c]quinoline derivatives were discovered to be a lead compound with highly analgesic activities. Based on the SAR of tetrahydropyrrolizino[2, 1-c]quinoline derivatives and Oripavine analgesic agents, twenty new compounds of 4-(1H-pyrrol-2-yl)-tetrahydroquinoline derivatives were designed and synthesized. Their chemical structures were characterized by ~1H-NMR and MS.Acid-induced mice writhing was used to evaluate the analgesic activity. Pharmacological studies showed that most of the synthesized compounds displayed notable analgesic activities at a dose of 200 mg/kg. The activities of compounds FLY-1, FLY-6, FLY-12, FLY-14, FLY-15 are comparable to that of morphine at a dose of 10 mg/kg. They could be regarded as valuable compounds for further study. Some new SAR of these compounds was summarized.更多还原