A series of novel thiadiazoles bearing pyrido [2,3-d] pyrimidinone moiety were synthesized by reaction of 2-(4-oxo-5, 7-di-p-tolyl-3, 4-dihydropyrido [2,3-d] pyrimidin-2-yl)-N-phenylhydrazine carbothioamide with a variety of hydrazonoyl chlorides in ethanol containing catalytic amount of triethylamine. Also, a novel pyrazolinone containing pyridopyrimidinone moiety was prepared by treating 2-hydrazinyl-5, 7- di-p-tolylpyrido [2,3-d] pyrimidin-4 (3H) one with ethyl acetoacetate, and was utilized for synthesis of some new arylidene- and arylazo pyrazolinone derivatives. The structure of all the new products was established by elemental and spectroscopic analysis. The mechanisms of the studied reactions were also discussed. The antitumor activity of nine of the synthesized compounds was estimated versus MCF-7 cell line and the outcomes showed that some of them revealed powerful activity. In addition, the relation between the structure and the activity has been discussed.