Synthesis And Antitumor Activity Evaluation Of Thienopyrimidine And Thienopyridopyrimidine Derivatives

After being found to show widespread antitumor activities, thienopyrimidinederivatives and thienopyridopyrimidine derivatives have attracted increasing attentionand played an important role in the development of novel antitumor drugs. Some ofthese compounds were synthesized as novel epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors. In this paper a series of novel thieno[2,3-d]pyrimidinederivatives and thieno[3’,2’:5,6]pyrido[4,3-d]pyrimidine derivatives have beendesigned and synthesized via Gewald reaction under mild condition. Furthermore, theircyclization conditions, spectral properties and biological activities have been explored.In this dissertation, five series of compounds which containing forty-threeunreported were designed and synthesized, there structures have been confirmed by IR,1H NMR,13C NMR, MS. All the structural formulas of them are as follows:I.3-alkyl-7-methyl-5,6,7,8-tetrahydro-3H-pyrido[4’,3’:4,5]thieno[2,3-d]pyrimidin-4-one (4a~4c,3) All compounds were tested in vitro antitumor activities. Among them compounds16a10g,10l,16a and16j showed good in vitro antitumor activities, expecially thecompound16a which showed more potent inhibition of KB and CNE2than5-FUcould be synthesized in large quantities for in vivo antitumor activity research. Thus,these five compounds could be further modified to obtain the compounds with morepotent antitumor activity.