Synthesis and antitumor activity of new pyrido[2,3-d]pyrimidine derivatives

New series of pyrido[2,3-d]pyrimidines such as; 5-(4-aryl-5-sulfanyl-4H-[1,2,4]triazol-3-yl) 1H,3H,8H-pyrido[2,3-d]pyrimidine-2,4,7-triones 6, 7; S-[3-(2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl)-4-(4-substituted phenyl)-4H-[1,2,4]triazol-5-yl]-2-(4-phenylpiperazin-1-yl)ethanethioates 10, 11; 2,4,7-trioxo-N'-[(4-substituted piperazin-1-yl)acetyl]-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazides 13-16 and N'-arylidene-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazides 17-19 was synthesized through the reaction of the key intermediate 2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-5-carbohydrazide 3 with different reagents. The structures of the newly synthesized compounds were elucidated through microanalysis, IR, H-1 NMR, C-13 NMR, and mass spectroscopy. These compounds have been subjected to in vitro antitumor evaluation by bleomycin-dependant DNA damage assay. The most active antitumor compound 6 was selected for further in vivo evaluation of antineoplastic activity against Ehrlich ascites carcinoma in mice. It was observed that our target compound has a potent antitumor activity.