ABSTRACT
A series of 4-(N-aryl)amino-6-alkoxyl pteridine derivatives was designed and synthesized via the bio-isostere principle using anti-cancer drugs with quinazoline cores as lead compounds.The proliferative inhibitory activities of the synthesized compounds against tumor cells A549,KG1a and HGC-27 were also performed by MTT assay.Using methyl 3-aminopyrazine-2-carboxylate as the starting material,12 target compounds(7a-7l)were synthesized through six-step reaction, and characterized by 1H NMR, 13C NMR and MS.It was showed that antitumor activity of pteridines with 2-chloro-5-nitro-anilino substituted in position 4 was more potent than that of others.The activity of compound 7b on A549 cells(IC50=11.55 μmol/L)was closely approximate to that of positive control gefitinib(IC50=5.95 μmol/L).IC50values of compound 7k on three cell lines were all close to those of gefitinib.A 2-chloro-5-nitro-anilino fragment was contained in preferred compounds which might be modified for further investigation.