Research On Synthesis And Biological Activity Of 4H-Pyran And Quinoxaline Derivatives

Aromatic heterocycte compounds that containing Oxygen and nitrogen have been widely used for antitumor,antibacterial,antiviral and anti-inflammatory.It has become a hot field of new drug research.Among them The 4-aryl-4H-pyran and quinoxaline derivatives have their own unique antibacterial and antitumor mechanism.The 4-aryl-4H-pyran derivatives of natural product have been found that they can bind to the Colchicine-binding site or the adjacent site of tumor cells,so as to inhibit the activity of tubulin,resulting to the apoptosis of tumor cells.In chapter 1 of this paper,we use the principle of skeleton transition and local modification,using the 4-aryl-4H-chromene as a leading compound,designing a series of 4-aryl-4Hchromene derivative.In chapter 1,substituted benzaldehyde was reacted with malononitrile by knoevenagel condensation,Obtaining innamonitrile derivatives.Then the innamonitrule derivatives were cyclizated with ?-keto-ester derivatives,obtaining targate coupound.Twenty-five 4H-pyran cpmpounds(20a-20 j,21a-21o),have been synthesized in total.And their structure were all confirmed by IR,1H-NMR,part of them were confirmed by13C-NMR?MS.Human hepatoma cell BL7402 was selected for testing the antitumor activity of compound 20a?20b?20c?20d?20e?20f?20g?20h?21b?21c and 21 n by MTT.Among them there were nine compounds,activity better than Positve-effect drug-5-Fu.Especially compound 20b?20g?21b showed good pharmacological activity in vitro,and the IC50 of the three against BL7402 were respectively 24.04?mol /L ?38.20?mol/L ? 21.3?mol/L,5.75 ? 1.61 ? 6.47 times than 5-Fu especially.The structure-activity-relationship(SAR)of this category compound was preliminary analysized.In addition,5-F-2-Nitro aniline was used as a starting material.It was nucleophilic substituted by L-prolinol.Then the product was reducted by Pd/C-HCOONH4,obtaining 4-L-prolinol o-diaminobenzene.O-diaminobenzene derivative was cyclizated by ?-Cl-Substituted Acetophenone,which was the nuclear parent of quinoxaline derivative.Then the nuclear was dehydration synthesized withsubstituted niacin,obtaining the target coupound.we have synthesized eight quinoxaline derivatives in total.The structure of the eight were all confirmed by IR,1H-NMR,Four of them were selected for antimicrobial test.