含噻唑环吡啶酮新型衍生物的合成及其抗肿瘤活性

发布时间：2018-06-14 23:41

  本文选题：吡啶酮 + 噻唑　； 参考：《湖南科技大学》2017年硕士论文

【摘要】：吡啶酮类化合物及其衍生物以其良好的药理与生物活性而成为当今医药界,农药界,化学界研究的热点。药理学研究表明:此类化合物因具有良好的抗肿瘤、抗阿尔茨海默病(Alzheimer disease,AD,即老年痴呆症)、抗菌、抗病毒、抗寄生虫以及预防肝纤维化等生物活性而被广泛应用于医药研究中;此外,随着近年来功能材料的兴起,吡啶酮及其衍生物在染料、热变色材料和感光材料等方面也有广泛的应用。噻唑环是一类含有N、S杂原子的五元杂环化合物。大量文献显示,含噻唑杂环结构的化合物也具有良好的生物活性,其特殊的结构使其可用于有机合成试剂,医药、绿色农药、橡胶促进剂和染料等领域。本文根据药物叠加原理,将噻唑环与吡啶酮结合起来,合成了12种新型5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮类化合物,并对合成条件进行了优化,从而得到较优的合成条件。对所合成的5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮类化合物的结构用IR,1H NMR,13C NMR,MS进行了表征,同时也初步研究了5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮类化合物的抗肿瘤生物活性。研究结果如下:1、以2,3-二羟基吡啶,不同取代基的苯胺,Na IO3为原料,利用氧化-迈克尔加成的方法,合成了12种中间产物5,6-二取代-2,3-吡啶二酮1,并对这些化合物的结构进行了表征,所得结果与文献值一致。2、在浓硫酸催化下,利用5,6-二取代-2,3-吡啶二酮1与硫代氨基脲反应,合成了12种中间产物5,6-二取代-2,3-吡啶二酮缩氨基硫脲衍生物2,并对这些化合物的结构进行了表征,所得结果与文献值一致。3、在冰醋酸催化下,利用5,6-二取代-2,3-吡啶二酮缩氨基硫脲衍生物2与3-氯-2,4-戊二酮反应,合成目标产物5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮3。并对该目标化合物5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮3的合成条件进行优化,得到合适的物质的量之比、反应时间、反应温度、催化剂选择和用量,即:以无水乙醇为溶剂,物质的量之比为1:2.0,催化剂冰乙酸的加入量为0.30m L,反应时间为3.5hour,反应温度设置为65℃。4、对所合成的部分目标产物5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亚联氨基吡啶-2-酮类化合物进行了抗肿瘤活性的测试,发现此类化合物对人结肠癌细胞HCT116,人胃癌细胞MGC-803,人肝癌细胞Huh7具有良好抑制活性。
[Abstract]:Pyridinone compounds and their derivatives have become a hot research area in the field of medicine, pesticide and chemistry because of their good pharmacology and biological activity. Pharmacological studies have shown that these compounds have been widely used in medical research because of their good anti-tumor, anti-Alzheimer disease AD-Alzheimer disease, that is, Alzheimer's disease, antibacterial, anti-virus, anti-parasitic and anti-liver fibrosis and other biological activities. In addition, with the development of functional materials in recent years, pyridone and its derivatives have been widely used in dyes, thermochromic materials and photosensitive materials. Thiazole ring is a class of quaternary heterocyclic compounds containing Nu S hetero atoms. A large number of literatures show that the compounds with thiazolium heterocyclic structure also have good biological activity, and their special structure makes them useful in the fields of organic synthesis reagents, medicine, green pesticides, rubber accelerators and dyes. Based on the principle of drug superposition, twelve novel 5-azole-6-disubstituted -3-trimethyl-4-methyl-5-acetylthiazole-2-yl) pyridine-2-biaminopyridyl compounds were synthesized by combining thiazolyl ring with pyridinone, and the synthetic conditions were optimized. Thus, the optimal synthetic conditions are obtained. The structure of the synthesized 5o 6-disubstituted -3-methyl-5-acetylthiazole-2-yl) aminopyridine 2-one compounds was characterized by IR 1H NMR-13C NMRMS, and the structure of the synthesized compounds was characterized by IR 1H NMR-13C NMRMS, and the structure of the compounds was characterized by IR 1H NMR-13C NMRMS. At the same time, the antitumor biological activity of 5o 6-disubstituted-3-o-4-methyl-5-acetyl-thiazolyl)-2-bibiaminopyridine-2-one compounds was also studied. The results of the study are as follows: 1. Using 2o 3-dihydroxy pyridine and aniline dihydroxypyridine with different substituents as raw materials, the oxidation-Michael addition method was used. Twelve intermediates, 5o 6-disubstituted -2o 3-pyridine diketone 1, were synthesized, and their structures were characterized. The results were in agreement with the reference value of .2.The reaction of 5o 6-disubstituted -2-pyridine-3-pyridine-1 with thiosemicarbazone was carried out under the catalysis of concentrated sulfuric acid. Twelve intermediates, 5o 6-disubstituted -2pyridine-3-pyridinone thiosemicarbazone derivatives, were synthesized, and their structures were characterized. The results were in agreement with the results in literature. The results were in agreement with the results in the presence of acetic acid in the presence of glacial acetic acid. In this paper, the target product, 5o 6-disubstituted -3-methyl-5-acetylthiazole-2-yl) -2-biaminopyridine-3-one, was synthesized by the reaction of 2-thiosemicarbazone derivative 2 with 3-chloro-2-pyridine-4-pentanedione. The optimum conditions for the synthesis of the target compound 5o 6-disubstituted -3-thiazolyl 4-methyl-5-acetylthiazole-2-yl) pyridine-2-one were obtained, and the appropriate mass ratio, reaction time, reaction temperature, catalyst selection and dosage were obtained. That is, using anhydrous ethanol as a solvent, The molar ratio of material is 1: 2.0, the amount of acetic acid is 0.30 mL, the reaction time is 3.5hourling, the reaction temperature is 65 鈩，

本文编号：2019497