SYNTHESIS OF NOVEL [1,2,4]TRIAZOLO[3,4-B][1,3,4]THIADIAZOLE-6(5H)-THIONE, 5,8-DIHYDRO-[1,2,4] TRIAZOLO[4,3-B][1,2,4,5]TETRAZINE AND 5,10-DIHYDRO -[1,2,4]TRIAZOLO[4,3-B][1,2,4] BENZOTRIAZINE DERIVATIVES AND STUDY THEIR BIOLOGICAL ACTIVITY.

Nitrogen-containing heterocycles are of particular interest and significant importance for the discovery of potent bioactive agents in pharmaceutical industry. The present study reports the synthesis of new heterocycles including 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives (2, 6, 8a,c,9a,b,10a, and 11a,b) by cyclocondensation reaction of 1a-cwith CS2, ethylcyanoacetate, cyclohexanone, ethyl chloroformate, trichloroacetic acid and oxalic acid scheme (1,2).[1,2,4]triazolo[4,3-b][1,2,4, 5]tetrazine derivative13 was prepared by the reaction of 4-amino-5-substituted-4H-1,2,4-triazole-3-thiol 1b with hydrazine hydrate followed by cyclocondensation with para-chlorobenzaldehyde scheme (3).[1,2,4]triazolo[4,3-b][1,2,4] benzotriazine derivative 14 which prepared by cyclocondensation of 1b with ortho-aminothiophenol scheme (3).The structures of newly synthesized compounds were characterized by IR, 1H NMR and mass spectral data. Some of These compounds (7, 8c, and 9a) were exhibited significant growth inhibition against (HepG2) cancer cell line when screened for their in vitro cytotoxic activity against human hepatocellular liver carcinoma (HepG2). The results of such studies are discussed in this paper.