Dissertation
Dissertation > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry

Synthesis and Bioactivity Research of New Quinazoline Compounds

Author LiuGang
Tutor SongBaoAn
School Guizhou University
Course Pesticides
Keywords quinazoline anthranilic acid gallic acid synthesis antifungal activities anticancer activities biological activity
CLC R914
Type PhD thesis
Year 2006
Downloads 598
Quotes 4
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In recent years, quinazoline compounds take on good biological activity in medicine and pesticide aspect. With synthesis and bioactivity study of quinazoline compounds developing, it’s become one of a focuses studied field to chemicals and biological scholars. In medicine aspect, quinazoline compounds have inhibition on EGF receptor (EGFR), and then demonstrate the anticancer activation. In addition, quinazoline compounds still resist malaria and HIV, treat benign prostate gland hyperplasia and loose. In pesticide respect, quinazoline oxime ether compounds have good biological activity to anti-TMV, CMV and fungal.In order to create more high-efficient anticancer medicine or fungicide, look for the new target which treats cancer or plant fungicide, guide and develop the new target medicine or pesticide to treat cancer or plant fungicide, regarding PD 153035 as the leading compound, we design and synthesize four kinds of new-type quinazoline compounds: (Ⅰ) Anthranilic acid taken as raw materials, cycled by fonnamide, chlorined by phosphorus pentachloride and phosphorus oxychloride, and then reacted with aryl amine to get N-substituted-4-aminequianzoline, 15 compounds are synthesized. The structure of all 15 compounds is characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. (Ⅱ) Take anthranilic acid as raw materials, we get 5-chlorine-2-aminobenzoic acid or 3,5-dichlorine-2-aminobenzoic acid after single chlorination or double chlorination. Then, the 5-chlorine-2-aminobenzoic acid or 3,5-dichlorine-2-aminobenzoic acid through cycled by formamide, chlorined by phosphorus pentachloride and phosphorus oxychloriden, and then reacted with aryl amine to get chlorine substituted N-substituted-4-aminequianzoline. Finally, 6 compounds are synthesized. The structure of all 6 compounds is characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. (Ⅲ) Gallic acid taken as raw materials, ethered by dimethyl sulfate, estered by menthol, nitrated by nitric acid, hydrolized in base, reduced by tin dichlorine, cycled by formamide, chlorined by phosphorus oxychloride, and reacted with aryl amine to get 6,7,8-trimethoxyl N-substituted-4-aminequianzoline, 19 compounds are synthesized. The structure of all 18 compounds is characterized by IR, 1H NMR, 13C NMR and elemental analysis. (Ⅳ) 4-Chlorine quinazoline compound reacted with sulphur aryl phenol in potassium carbonate and acetone, S-substituted-4-sulphur ether quinazoline are synthesized. The structure of all 7 compounds is characterized by IR, 1H NMR, 13C NMR and elemental analysis. 47 title compounds are synthesized in total.The synthetic methods of the intermediate and title compounds are decrepit. Particularly, the synthesis of key intermediate 2-amino-3,4,5-trimethoxyl benzoic acid is explained in detail. In addition, we explore 2-methyI-6,7,8-trimethoxyl-quinazolin-4-one via the reaction of 2-amino-3,4,5-trimethoxyl benzoic acid with acetic anhydride, through 6,7,8-trimethoxy-2-methyl-benzo [d][1,3]oxazin-4-one.The present new method of the formation of N-substituted-4-aminoquinazoline derivatives under microwave irradiation offers several advantages: faster reaction rates and higher yields, which involves a reduction of reaction time from 12 h to 20 min and a raise in yields from 24.451.3% to 79.196.5%, compared with the classical method.Some title compounds and intermediate suppressing fungicide such as Fusarium graminearum, Cytospora mandshurica and Fusarium oxysporum is tested. The result indicates that some compounds have good activation of suppressing antifungal activities respectively such as I12. When the medicament concentration is 500 μg/mL, suppression ratio of the compound I12 is

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