Study On Synthesis And Antitumor Activity Of Amino Acid Ester Derivatives Containing Thieno [3,2-d] Pyrimidine Moiety

Thieno[3,2-d]pyrimidine is a kind of important nitrogen-sulfur heterocyclic compounds,its derivatives were widely used in the development and screening of new drug due to their broad spectrum of biological and pharmaceutical activities such as anti-cancer,anti-bacterial,anti-malarial,antioxidant and anti-virus,etc.At the same time,amino acid esters plays a pivotal role in medicine,chemicals,agriculture and food too.They can be used for the synthesis of pharmaceutical intermediates,sterile insecticides,food additives,and have high application value in the fields of medicine and pesticides.According to the principle of superposition of drug molecules,we introduced thieno[3,2-d]pyrimidine ring to the amino acid methyl ester that led to generate structurally novel thienopyrimidine series derivatives?A1-A15 and B1-B15?.The synthetic route is shown in Scheme 1.The new 30 target compounds have not been reported in literature,and the structures of all the compounds were confirmed by 1H NMR,13 C NMR,HRMS and IR.The antitumor activities of these target compounds were investigated against human breast cancer MCF-7 cells by MTT assay.Results revealed that most compounds of the A-series showed moderate inhibitory activity,and the inhibitory rate of A13 and A14 could reach 64%.However,almost all the compounds of B-series had a weak inhibitory effect,with only B13 inhibition rates of58.5%.The IC₅₀ value of A13,B13 were 44.60 ?mol/L,45.79 ?mol/L,respectively.And the anti-MCF-7 activity was weaker than the positive control 5-FU.