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 acc omplished by the condensation of the benzoxazine I with 4-aminoacetoph enone. The semicarbazone III was obtained from II by refluxing with an equimolar amount of semicarbazide hydrochloride in ethanol. The latte r compound was then subjected to oxidative cyclization either by thion yl chloride or selenium dioxide to give thiadiazole and selena derivat ives IV and V, respectively. Compound V was condensed with different a romatic amines to yield the corresponding Schiff's bases VI. The pheny lglyoxal 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 derivat ive VIII. Treatment of II with bromine in acetic acid gave the bromo d erivative IX which was reacted with thiourea to give 2-amino-thiazole derivative X. Cyanopyridine-2-(1H)-thione derivatives XIVa-h were obta ined via the reaction of arylmethylenecyanothioacetamide XI with activ e 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 o f the non viable tumor cells to about 40% and 80% at concentration of 10 and 100 ng, respectively.