本文選題：吡啶酮 + 噻唑��； 參考：《湖南科技大學(xué)》2017年碩士論文

【摘要】：吡啶酮類化合物及其衍生物以其良好的藥理與生物活性而成為當(dāng)今醫(yī)藥界,農(nóng)藥界,化學(xué)界研究的熱點(diǎn)。藥理學(xué)研究表明:此類化合物因具有良好的抗腫瘤、抗阿爾茨海默病(Alzheimer disease,AD,即老年癡呆癥)、抗菌、抗病毒、抗寄生蟲(chóng)以及預(yù)防肝纖維化等生物活性而被廣泛應(yīng)用于醫(yī)藥研究中;此外,隨著近年來(lái)功能材料的興起,吡啶酮及其衍生物在染料、熱變色材料和感光材料等方面也有廣泛的應(yīng)用。噻唑環(huán)是一類含有N、S雜原子的五元雜環(huán)化合物。大量文獻(xiàn)顯示,含噻唑雜環(huán)結(jié)構(gòu)的化合物也具有良好的生物活性,其特殊的結(jié)構(gòu)使其可用于有機(jī)合成試劑,醫(yī)藥、綠色農(nóng)藥、橡膠促進(jìn)劑和染料等領(lǐng)域。本文根據(jù)藥物疊加原理,將噻唑環(huán)與吡啶酮結(jié)合起來(lái),合成了12種新型5,6-二取代-3-(4-甲基-5-乙�；邕�-2-基)亞聯(lián)氨基吡啶-2-酮類化合物,并對(duì)合成條件進(jìn)行了優(yōu)化,從而得到較優(yōu)的合成條件。對(duì)所合成的5,6-二取代-3-(4-甲基-5-乙�；邕�-2-基)亞聯(lián)氨基吡啶-2-酮類化合物的結(jié)構(gòu)用IR,1H NMR,13C NMR,MS進(jìn)行了表征,同時(shí)也初步研究了5,6-二取代-3-(4-甲基-5-乙酰基噻唑-2-基)亞聯(lián)氨基吡啶-2-酮類化合物的抗腫瘤生物活性。研究結(jié)果如下:1、以2,3-二羥基吡啶,不同取代基的苯胺,Na IO3為原料,利用氧化-邁克爾加成的方法,合成了12種中間產(chǎn)物5,6-二取代-2,3-吡啶二酮1,并對(duì)這些化合物的結(jié)構(gòu)進(jìn)行了表征,所得結(jié)果與文獻(xiàn)值一致。2、在濃硫酸催化下,利用5,6-二取代-2,3-吡啶二酮1與硫代氨基脲反應(yīng),合成了12種中間產(chǎn)物5,6-二取代-2,3-吡啶二酮縮氨基硫脲衍生物2,并對(duì)這些化合物的結(jié)構(gòu)進(jìn)行了表征,所得結(jié)果與文獻(xiàn)值一致。3、在冰醋酸催化下,利用5,6-二取代-2,3-吡啶二酮縮氨基硫脲衍生物2與3-氯-2,4-戊二酮反應(yīng),合成目標(biāo)產(chǎn)物5,6-二取代-3-(4-甲基-5-乙�；邕�-2-基)亞聯(lián)氨基吡啶-2-酮3。并對(duì)該目標(biāo)化合物5,6-二取代-3-(4-甲基-5-乙�；邕�-2-基)亞聯(lián)氨基吡啶-2-酮3的合成條件進(jìn)行優(yōu)化,得到合適的物質(zhì)的量之比、反應(yīng)時(shí)間、反應(yīng)溫度、催化劑選擇和用量,即:以無(wú)水乙醇為溶劑,物質(zhì)的量之比為1:2.0,催化劑冰乙酸的加入量為0.30m L,反應(yīng)時(shí)間為3.5hour,反應(yīng)溫度設(shè)置為65℃。4、對(duì)所合成的部分目標(biāo)產(chǎn)物5,6-二取代-3-(4-甲基-5-乙�；邕�-2-基)亞聯(lián)氨基吡啶-2-酮類化合物進(jìn)行了抗腫瘤活性的測(cè)試,發(fā)現(xiàn)此類化合物對(duì)人結(jié)腸癌細(xì)胞HCT116,人胃癌細(xì)胞MGC-803,人肝癌細(xì)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，

本文編號(hào)：2019497