本文選題：吲哚　切入點：吲哚酮衍生物　出處：《天津科技大學》2014年碩士論文　論文類型：學位論文

【摘要】：在自然界中,吲哚雜環(huán)廣泛的存在,在人們生活的各個領域都扮演著重要的角色。吲哚酮是吲哚衍生物中十分重要的一類化合物,具有廣泛的生物活性。靛紅及其衍生物具有很好的抗腫瘤活性、抗細菌活性、抗真菌活性、抗病毒活性和抗HIV病毒活性等,其對中樞神經系統的作用也被廣泛的研究。雖然吲哚酮類化合物的1-位,3-位和苯環(huán)上的衍生物已有較多報道,但對吲哚酮1-位,3-位和5-位多位點修飾的報道較少,因此,本論文對N-芳基吲哚酮衍生物的1-位,3-位和5-位進行了設計和合成及生物活性的研究。本課題以靛紅(吲哚酮)或對溴苯胺為原料,共進行了六步反應,首先靛紅的1-位N上連接芳環(huán)基團,然后通過黃鳴龍還原反應還原靛紅3-位羰基,接下來通過Suzuki偶聯反應或heck反應對5位進行修飾。本論文共合成了78個化合物,其中52個未見報道,經1H NMR,1C NMR確證其結構。采用MTT法對58個目標化合物和重要中間體進行了抑制腫瘤細胞生長活性測試,活性測試選用了三種癌細胞：人肝癌細胞HepG2,人白血病細胞K562,人結腸癌細胞HT-29。MTT測試結果表明：3-位引入芐基后的活性要高于其前體,5-位上為H的化合物在變?yōu)锽r后活性明顯提升,1-位引入芳基后的活性能夠維持或稍有提高。其中化合物5-溴-3-(4-三氟甲基亞芐基)-1-(4-甲氧基苯基)二氫吲哚-2-酮對K562、 HT-29、HepG2的IC50值分別達到2.21μM、9.95μM和69.341μM。
[Abstract]:In nature, indole heterocycles exist widely and play an important role in all fields of human life. Indole is a very important class of compounds in indole derivatives. Indirubin and its derivatives have good antitumor, antibacterial, antifungal, antiviral, antiviral and antiviral activities, etc. The effects of indole on the central nervous system have also been extensively studied. Although there have been many reports on the 1- and 3-site of indole compounds and the derivatives on benzene ring, there are few reports on the modification of indole 3-site and 5-site multisite modification of indole. In this paper, the design and synthesis of 1-site 3-site and 5-site of N-aryl indoleone derivatives were studied. In this paper, we used indole (indole) or p-bromoaniline as raw materials, and carried out a six-step reaction. First, the aromatic ring group was connected to the 1-position N of indirubin, then the 3-position carbonyl of indirubin was reduced by Huang Minglong, and then modified by Suzuki coupling reaction or heck reaction. In this paper, 78 compounds were synthesized. 52 of them were confirmed by 1H NMRN 1C NMR. The inhibitory activity of 58 target compounds and important intermediates on tumor cell growth was tested by MTT method. Three kinds of cancer cells were selected for activity test: human hepatoma cell line HepG2, human leukemia cell line K562. the results of HT-29.MTT test of human colon cancer cell line showed that the activity of the benzyl group introduced into the cell line was higher than that of the compound with H at the 5- site of the cancer cell. The activity of 5-bromo-3-pyrrolidene 4-trifluoromethylbenzylidene) dihydroindole-2-one for K562and HT-29Hep G2 was 2.21 渭 M9.95 渭 M and 69.341 渭 M, respectively.
【學位授予單位】：天津科技大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914;R96

【共引文獻】

相關期刊論文 前2條

1 高文濤;徐良玉;李陽;聶成銘;;靛紅及取代靛紅在合成雜環(huán)化合物中的應用研究進展[J];化學研究與應用;2013年12期

2 高文濤;趙賓賓;趙鵬波;李陽;;N-取代-5-甲(乙)基吲哚酮的簡便合成[J];化學研究與應用;2014年05期

相關碩士學位論文 前3條

1 姜俊芬;中藥有效成分靛玉紅衍生物BIO聯合干細胞因子擴增人臍血造血干/祖細胞的研究[D];上海交通大學;2007年

2 唐立明;Isatin衍生物的合成及其抗驚厥、抗抑郁活性研究[D];浙江海洋學院;2014年

3 趙賓賓;含5-烷（氧）基靛紅骨架新型雜環(huán)化合物的合成與表征[D];渤海大學;2014年

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本文編號：1651012