Studies On The Synthesis And Biological Activity Of Dihydropyrimidine Derivatives Containing 1,3,4-Thiadiazole

Dihydropyrimidine is common skeleton structure in organic compounds,and its derivatives are widely used in pesticides and medicine.Numerous litera-tures report that such compounds have good anti-hypertensive,anti-inflamma-tory,anti-HIV,anti-convulsant and other biological activities.In addition,1,3,4-thiadiazole derivatives also have anti-epileptic,ascorbic acid,anti-bacterial and other biological activities due to their structural characteristics.Therefore,it is of great practical significance to develop novel dihydropyri-midines derivatives containing 1,3,4-thiadiazole with good biological activity.Based on the principle of superposition of biological activities,two series of new dihydropyrimidines derivatives containing 1,3,4-thiadiazole were designed and synthesized in this study,and the anticancer activity of some synthesized compounds were tested.The main contents and results of this study include:1.Study on the Synthesis of Dihydropyrimidine Derivatives Containing1,3,4-Thiadiazole（1）Using aromatic aldehydes,2,4-pentanedione,thiourea as raw materials,the compound 4-methyl-6-aryl-5-acetyl-2-mercapto-1,6-dihydropyrimidineⅠwas synthesized by Biginelli reaction.Using concentrated hydrochloric acid as catalyst,compoundⅠreacts with carbonothioic dihydrazide to obtain compound 1-（4-Methyl-6-aryl-2-mercapto-1,6-dihydropyrimidin-5-yl）ethenone-thiocarbaz-oneⅡ.Using glacial acetic acid as a catalyst,compoundⅡwas condensed under the action of triethyl orthoformate to obtain the compound 5-（1-（1,3,4-thiadia-zol-2-yl）hydrazide）ethyl)-4-methyl-6-aryl-2-mercapto-1,6-dihydropyrimi-dineⅢ.Under the catalysis of triethylamine,compoundⅢwas reaced with ethyl bromoacetate,and cyclized to obtain the target compound（E）-6-（1-（1,3,4-thia-diazol-2-yl）hydrazi-ne）ethyl)-7-methyl-5-aryl-5H-thiazolo[3,2-α]pyrimidin-3（2H）-oneⅣwere synth-esized.At the same time,the influence of catalyst type,reaction solvent,feed ratio,reaction temperature,reaction time on the reaction yield of the compounds were explored,and the structure of the compounds have been verified by IR,¹H NMR,^{1 3}C NMR,and ESI-MS.2.Study on the Biological Activity of Dihydropyrimidine Derivatives Containing 1,3,4-ThiadiazoleThe anticancer activity of compound（E）-6-（1-（1,3,4-thiadiazol-2-yl）hydraz-ine）ethyl)-7-methyl-5-aryl-5H-thiazolo[3,2-α]pyrimidin-3（2H）-oneⅣwere test-ed by MTT assay.The results show that some compounds have certain inhibitory activity against human esophageal cancer cells（EC-109）and adenocarcinoma cells（A549）,among which compoundⅣ-5 has better inhibitory activity than other compounds,but the inhibitory activity of all target compounds on human gastric cancer cells（MGC-803）was poor.