Nine novel heterozygous N-substituted isatin-quinazoline compounds(8a～8i)were synthesized using N'-(2-cyano-4-iodophenyl)-N,N-dimethylformamidine and isatin as the starting materials.Dimroth rearrangement of N'-(2-cyano-4-iodophenyl)-N,N-dlimiethylformamidine with arylamines,and subsequently Suzuki coupling with 2-formylfuran-5-boronic acid gave compounds 4a～4c.Meanwhile,compounds 7a～7c were synthesized by the substitution and hydrazone reactions of isatin at 1-position and 3-position,respectively.Finally,nine target compounds(8a～8i)were formed through nucleophilic addition reaction of 4a～4c and 7a～7c.The chemical structures of the synthesized compounds were characterized by NMR,IR and HRMS.The antitumor activities of these compounds on human colorectal carcinoma cells SW480,human epidermoid squamous carcinoma cells A431,human non-small cell lung cancer cells NCI-H1975 and A549 were tested through MTT method in vitro.The results indicated that most of the compounds had significant inhibition effect on the growth of tumor cells.Among which,compounds 8a,8b,8e,8g showed higher inhibitory activities on the proliferation of four cell lines than the positive controls of Lapatinib and Gefitinib.It can be seen that the activity of inhibiting tumor cell proliferation was good when the 4-position of quinazoline unit was 3-ethynylphenylamino,and compounds bearing 3-chloro-4-fluorophenylamino or 3-chloro-4-(3-fluorobenzyloxy)phenylamino at the 4-position of quinazoline unit also showed relatively good activity of inhibiting tumor cell proliferation.When the 5-position of isatin unit had no substituent or was substituted by F,the activity of inhibiting tumor cell proliferation was good,but the inhibiting activity was poor when the 5-position of isatin unit was substituted by Cl.
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