【作者】 张春波；

【导师】 朴虎日； 全哲山；

【作者基本信息】 延边大学 ， 药物化学， 2002， 硕士

【摘要】 尽管人类由心血管疾病引起的死亡率在下降，但由充血性心力衰竭（Congestive Heart Failure，CHF）间起的死亡率却还在上升。目前，在临床上尚无理想的有效治疗充血性心力衰竭的正性肌力药物。 为了寻找正性肌力作用更强、副作用较小的治疗充血性心力衰竭的正性肌力药物，1999年朴虎日等根据电子等排原理设计合成了取代哌嗪乙酰氨基喹啉酮衍生物20个，并从中筛选出了具有较强正性肌力活性、同时具有扩血管作用，对心率影响甚微且选择性很高的化合物PHR960012。 2000年朴虎日等又以PHR960012为先导化合物，改变苄基苯环上的取代基，设计合成了14个取代苄哌嗪乙酰氨基喹啉酮衍生物，其中8个化合物体外实验中显示比米力农更强的正性肌力活性。其中PHR9903和PHR9906的活性非常显著。 本文综合分析了有关二氢喹啉酮类化合物的结构与正性肌力活性的文献报道，在喹啉环上并入三氮唑并改变哌嗪环和三唑环上的取代基，设计合成了19个4，5二氢－［1，2，4］－三氮唑并［4，3－a］喹啉衍生物，探索其并入三唑环及不同取代基对活性的影响。其结构经质谱、红外光谱和核磁共振氢谱确证。其中化合物0006，0008，0010，0013，0017，0019有血管舒张活性。 本课题意义在于：合成了19个未见报道的4，5二氢－［1，2，4］－三氮唑并［4，3－a］喹啉衍生物，并为探讨在喹啉环上并入三唑环对活性的影响成为可能。更多还原

【Abstract】 Generally speaking,the mortality caused by angiocardiopathy is declining every year,but the mortality caused by congestive heart failure (CHF) is rising steadily and there is short of effective drugs for CHF in clinic up till the present moment.In order to developing more effective positive inotropic agents having lower side effects,Huri Piao et al reported the synthesis and the positive inotropic activities of 20 4-substitutedpiperazine-1 -acetamido-3,4-dihydroquinolinone derivatives using the principle of isosterism through investigating and analysing the structure and the activities of reported 3,4-dihydroquinolinone derivatives,among which the PHR960012 has been screened and showed the moderate positive inotropic activity followed angiectatic effect and high selectivity (having few effects on the heart rate) in 1999.A series of substituents on the benzene ring of the benzyl group on the PHR960012 which was considered as a lead compound were investigated and the corresponding 14 compounds were synthesized by Huri Piao et al. in2000. The biological tests showed that 8 compounds exhibited stronger activities compared to Milinone and compounds PHR9906 and PHR9903 showed the most significant positive inotropic activities among those compounds.In this paper,a triazole ring being added to the quinoline ring and 19 compounds with different substituents on both rings were synthesized in this paper. Their structures were confirmed by MS,IR,and 1HNMR .更多还原