Studies On The Syntheses And Antitumor Activities Of Two Types Of Azoles Compounds

Heterocyclic rings are an important type of organic compounds,which play essential roles in the life movement process.Being one kind of the heterocyclic rings,azoles compounds have significant implications for both of researches and applications,not only in the aspect of biology,but also in the fields of organic catalysis,photo-electronic functional materials and so on.In this context,the azoles compounds have long been one of hotspots in the heterocyclic rings researches.This thesis is dedicated to the study of the oxazoles and pyrazoles in azoles compounds family.Firstly,the progress of the syntheses and bioactivities for above two azoles were analyzed and discussed.On the one hand,most of the reported syntheses methods for oxazoles usually need strictly reactive conditions,such as high reaction temperature and long reaction time,complex operations,expensive precious metal catalysts,while resulted in low yields and limited tolerance.Thus it is important significance to explore an easy,rapid,high yielded and selective synthesis method for oxazoles.On the other hand,a number of pyrazoles were found to show excellent antibacterial and antitumor activities,which are regarded as important active groups for the syntheses of drugs with high bioactivities.This imply that it is hopeful expected to achieve breakthroughs in the bioactivities through the structures modification or introduction of other active groups based on pyrazoles parents.On account of above reasons,we set out to study the synthesis methods and the bioactivities of oxazoles and pyrazoles based on previous works and development direction of our group,and finally synthesized eighteen 2-aryl benzoxazoles and nine secnidazole 1,5-diaryl substituted pyrazole-3-carboxylates.It should be noted that the study for first the series compounds is emphasized on the exploration for the synthesis method of the optimization of the catalytic system,while the latter focuses on the antitumor activities of the obtained pyrazoles.The mail content of the thesis is as follows:1.A high efficient synthesis method for 2-aryl benzoxazoles was developed base on o-aminophenol and aromatic aldehydes substrates with a Cu(OTf)2-PhCl catalytic system.This method takes advantage of mild condition,rapid reaction rates,inexpensive substrates,good tolerance and atom economy,which could be used to achieve 2-aryl benzoxazoles bearing various substituted groups.The proposal mechanism conclude that the reaction of this type gone through a tandem reaction process including condensation,cyclization and oxidation under the Cu(OTf)2-PhCl catalytic system.2.On the basis of combination principle of the drugs,a series of secnidazole 1,5-diaryl substituted pyrazole-3-carboxylates were synthesized.All targeted compounds were structurally characterized by NMR,ESI-MS and elemental analysis,and their antitumor activities were further investigated.The results indicated that all compounds have significant inhibitory activities against the human lung cancer cell line NCI-H460,gastric cancer cell line MCG-803,ovarian cancer cell line Skov-3 and liver cancer cell line BEL-7404.Among these compounds,9fc show the best inhibitory activities against the first three cell lines with the IC50 values of 1.34,0.14 and 0.87 μM,respectively.While 9bc display the best inhibitory activity against liver cancer cell line BEL-7404 with the IC50 value of 5.34 μM.These inhibitory activities are all superior to those of cis-platinum,a representative anticancer drug.However,their inhibitory activities against normal human liver cell line HL-7702 are comparable to that of cis-platinum.In addition,the antitumor mechanisms of 9fc and 9bc were further investigated.