Synthesis of some new thiadiazole selena, triazine, thiazole and cyanopyridine derivatives with assay for their antitumor activity

The synthesis of 2-methyl-3-(4'-acetylphenyl)quinazol-4-one II was accomplished by the condensation of the benzoxazine I with 4-aminoacetophenone. The semicarbazone III was obtained from II by refluxing with an equimolar amount of semicarbazide hydrochloride in ethanol. The latter compound was then subjected to oxidative cyclization either by thionyl chloride or selenium dioxide to give thiadiazole and selena derivatives IV and V, respectively. Compound V was condensed with different aromatic amines to yield the corresponding Schiff's bases VI. The phenylglyoxal derivative VII was prepared by oxidation of II with selenium dioxide. Condensation of VII with thiosemicarbazide in ethanol in the presence of potassium carbonate gave 3-mercapto-1,2,4-triazine derivative VIII. Treatment of II with bromine in acetic acid gave the bromo derivative IX which was reacted with thiourea to give 2-amino-thiazole derivative X. Cyanopyridine-2-(1H)-thione derivatives XIVa-h were obtained via the reaction of arylmethylenecyanothioacetamide XI with active methylene carbonyl compound II. Assay for antitumor activity showed that compound XIVc has a significant activity against Ehrlich Ascites Carcinoma tumor cells (in vitro) and displayed a significant percent of the non viable tumor cells to about 40% and 80% at concentration of 10 and 100 ng, respectively.