The Synthesis And Activity Researching Of 3,4-Two-Hydrogens-Quinazoliones

The development of anticancer drugs has been the focus of scientists, especially the development of novel structure, small and toxic side effects of anti-cancer drugs has become the focus of research content. According to the latest reports, quinazoline derivatives exhibit a broad spectrum of encouraging antitumor and antifungal activities. So at present, the synthetic and structural design of the synthetic and structural design of the.But these methods are often confined to the non chiral synthesis, and have the disadvantage of low yield.In this paper, we use four chapters for introduceing the quinazolinone derivatives:research background, synthetic methods and application of activated. The main access to the following results:In the synthesis: the use of the format of R1, R2 for the substrate expansion; in the third step reaction, the first hydroxyl group into the carbonyl group and then to the synthesis of amino acid synthesis route. First with the PCC oxidation, and then the reduction reaction with iron powder / hydrochloric acid method, this method has the advantages of simple operation, mild reaction and yield is up to 95%; the four step reaction to imines by microwave method, and then(S+) tert Ding Jiya sulfonamide and(R+) TERT Ding Jiya sulfonamide as a chiral inducer, synthesis of the two different chiral substrate;then the Chan Lam cross coupling and Buchwald Hartwig coupling method for formation of carbon nitrogen bond coupling product; income coupling products by BTC(three chlorine methyl carbonate) of intramolecular cyclization, eventually we successfully synthesized 27 chiral quinazolinone derivatives.In anti tumor activity test: test cells A549 lung cancer cells, K562 cells(leukemia), U251 glioma cells), BEC720E(gastric cancer cells), BEL7402 cell line(HepG2) SW1990 pancreatic cancer cells). Test method using MTT method. According to the activity of test results, we found that(S+) tert butyl thionylaniline synthesis of quinazoline showed good antitumor activity, and(R+) tert butyl thionylaniline quinazoline compounds have almost no activity, reminding us that in the future work of Chinesemedicine attention when chiral; the quinazolinone into CABBEEN, the activity has not improved, indicating that the structure of the carbonyl group is very important for activity;as for when the fluorine chlorine R2 inhibitory activity of K562 cells was significantly more than the other series of compounds that affect high fluorine atom antitumor activity;R3 inhibitory activity for the aliphatic substituents were more than the other High compound.