4-甲氧基-1，3-苯二磺酰胺衍生物的合成及体外抗血小板聚集活性测定
发布时间：2018-07-27 17:20
【摘要】：本文综述了血栓病的形成机制和危害，介绍了抗血小板聚集药物研究的意义及发展前景。 运用新药设计原理以及生物电子等排原理，在实验室前期的研究工作基础上，以通过体外抗血小板聚集反应活性初筛试验选出的N1, N3-二-(4-乙酰基苯基)-4-甲氧基-1,3-苯二磺酰胺为先导化合物，通过对吡考他胺两个1,3-侧链进行改造，设计并合成了17种4-甲氧基-1,3-苯二磺酰胺类化合物P1~P17，其中10种未见文献报道。对新近制得化合物进行了IR和1H NMR等光谱表征分析及熔点测定，部分目标化合物经质谱确认。 采用Born比浊法，对17种目标化合物进行的体外抗血小板聚集反应活性初筛试验结果表明，8种目标化合物表现出不同程度的抗血小板聚集活性，高于阳性对照药吡考他胺(Picotamide)和阿司匹林，其中化合物P13的活性最高，IC50值为0.46。 对较高活性的化合物P10，P13，P15和P17进行急性毒性试验，结果表明四种受试物都表现出较低的毒性，有进一步研究开发的价值。继续对化合物P10、P13和P15进行与L929细胞的作用研究，实验结果显示，三种受试物在中高给药浓度下细胞存活率均相对较高，进一步证明了目标化合物具有较低的毒性。根据药理试验结果，对目标化合物的构效关系做出初步的推测和总结，，为实验室今后类似研究工作提供了新的依据和参考。
[Abstract]:In this paper, the mechanism and harm of thrombosis were reviewed, and the significance and development prospect of antiplatelet aggregation drugs were introduced. Using the principles of new drug design and the principle of equal arrangement of biological electronics, on the basis of the preliminary research work in the laboratory, Using N _ 1, N _ 3-di-(4-acetylphenyl) -4-methoxy-3-benzenesulfonamide as a lead compound, two 1o 3- side chains of picotadamine were modified by the primary screening test of antiplatelet aggregation reaction activity in vitro. Seventeen kinds of 4-methoxy -1o 3-benzenedisulfonamide compounds P _ (1) P _ (17) have been designed and synthesized, of which 10 have not been reported in literature. The newly synthesized compounds were characterized by IR and 1H NMR spectra and the melting point was determined. Some of the target compounds were confirmed by mass spectrometry. Born turbidimetric assay was used to screen the antiplatelet aggregation activity of 17 target compounds in vitro. The results showed that 8 target compounds showed different degree of antiplatelet aggregation activity. The activity of compound P13 was higher than that of picotadine (Picotamide) and aspirin, and the highest activity of compound P13 was 0.46. The acute toxicity tests were carried out on the high activity compounds P10, P13, P15 and P17. The results showed that the four tested compounds showed lower toxicity, and were valuable for further research and development. The effects of compounds P10, P13 and P15 on L929 cells were further studied. The results showed that the cell survival rate of the three compounds was relatively high at medium and high concentrations, which further proved that the target compounds had lower toxicity. Based on the results of pharmacological tests, the structure-activity relationship of the target compounds was preliminarily speculated and summarized, which provided a new basis and reference for similar research in laboratory.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
本文编号：2148580
[Abstract]:In this paper, the mechanism and harm of thrombosis were reviewed, and the significance and development prospect of antiplatelet aggregation drugs were introduced. Using the principles of new drug design and the principle of equal arrangement of biological electronics, on the basis of the preliminary research work in the laboratory, Using N _ 1, N _ 3-di-(4-acetylphenyl) -4-methoxy-3-benzenesulfonamide as a lead compound, two 1o 3- side chains of picotadamine were modified by the primary screening test of antiplatelet aggregation reaction activity in vitro. Seventeen kinds of 4-methoxy -1o 3-benzenedisulfonamide compounds P _ (1) P _ (17) have been designed and synthesized, of which 10 have not been reported in literature. The newly synthesized compounds were characterized by IR and 1H NMR spectra and the melting point was determined. Some of the target compounds were confirmed by mass spectrometry. Born turbidimetric assay was used to screen the antiplatelet aggregation activity of 17 target compounds in vitro. The results showed that 8 target compounds showed different degree of antiplatelet aggregation activity. The activity of compound P13 was higher than that of picotadine (Picotamide) and aspirin, and the highest activity of compound P13 was 0.46. The acute toxicity tests were carried out on the high activity compounds P10, P13, P15 and P17. The results showed that the four tested compounds showed lower toxicity, and were valuable for further research and development. The effects of compounds P10, P13 and P15 on L929 cells were further studied. The results showed that the cell survival rate of the three compounds was relatively high at medium and high concentrations, which further proved that the target compounds had lower toxicity. Based on the results of pharmacological tests, the structure-activity relationship of the target compounds was preliminarily speculated and summarized, which provided a new basis and reference for similar research in laboratory.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
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