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Cancer is a main reason for human morbidity and mortality globally. Screening and identifying new anticancer chemical substances is considered as a valid treatment for carcinoma. In our study on synthesis and search towards the development of potential anticancer agents, a series of thieno[2,3‐d]pyrimidine derivatives were prepared from the functionalized iminophosphorane via aza‐Wittig reaction. Their structures were confirmed by 1H NMR, 13C NMR, MS and elemental analysis. The in vitro antitumor activities of compounds were analyzed with CCK8 standard method. It revealed these thieno[2,3‐d]pyrimidine derivatives were exhibited cytotoxicity against HepG2, HEp‐2, and MCF‐7 cell lines. The most potent compounds, 5 h and 5 j, were efficacious against HEp‐2 cells with IC50 1.8μmol/L and 0.8μmol/L, respectively. Meanwhile, 5 a, 5 d and 5 h showed broad spectrum of cytotoxicity for HepG2, Hep2 and MCF‐7 three different cell lines with IC50 range of 1.8‐87.5μmol/L. Furthermore, we demonstrated that cytotoxicity of 5 j was due to the activation of caspase‐9 involved apoptotic pathway, which is death receptor independent. [ABSTRACT FROM AUTHOR]

Abstract: The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with ammonia to give ethyl 3,4-dihydro-6-methyl-4-oxo-2-arylamino-furo[2,3-d]pyrimidine-5-carboxylate 3. Further reaction of 3 with POCl3 and various amines generated ethyl 4-alkylamino-2-arylamino-6-methyl-furo[2,3-d]pyrimidine-5-carboxylate 5 in good yields. Their structures were confirmed by 1H NMR, EI-Ms, IR and elemental analysis. Compound 5b was further analyzed by single crystal X-ray diffraction. Compound 5 exhibited cytotoxicity against two lung cancer cell lines. For example, compound 5a showed the best inhibition activities against A459 with IC50 0.8μM. [ABSTRACT FROM AUTHOR]