Synthesis of pharmaceutically important condensed heterocyclic 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives as antimicrobials

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.

“…Ethyl-2-(3-(trifluoromethyl) [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazol-6-yl)acetate 6 was prepared by refluxing 4-amino-5-trifluor-methyl-4H-1,2,4-triazole-3-thiol 1 a with ethyl cyanoacetate in the presence of ortho phosphoric acid at 120 o C for 3 hours. Compound 6 was formed via nucleophilic addition of 1,2,4-triazole amino thiol derivative 1 a at the cyano group of ethyl cyanoacetate, followed by cyclization with elimination of ammonia.TheIR spectrum of 6 contained an absorption band at 1717 cm -1 , typical of ester carbonyl.…”

“…For this reason, much attention has been directed in our laboratory for synthesis of new compounds containing [1,2,4]triazole nucleus fused with a different substituted [1,3,4] thiadiazole, [1,2,4,5]tetrazine and [1,2,4] triazine moieties, in order to study their anticancer activity.…”

“…The chemistry of 1,2,4-triazoles and their fused heterocyclic derivatives have received considerable attention owing to their synthetic and effective biological importance. For example, a large number of 1,2,4-triazoles have been incorporated into a wide variety of therapeutically interesting drug candidates possessing antimicrobial [1][2][3][4][5], anti-inflammatory [6], analgesic [7] and anticancer activities [8,9]. Among these heterocycles, the mercapto and thione substituted 1,2,4-triazole ring systems have been well studied and so far a variety of biological activities have been reported for a large number of their derivatives [10,11].…”

“…The present study reports the synthesis of new heterocycles including 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives (2, 6, 8 a,c ,9 a,b ,10 a , and 11 a,b ) by cyclocondensation reaction of 1 a-c with CS 2 , 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 1 b with hydrazine hydrate followed by cyclocondensation with parachlorobenzaldehyde scheme (3). [1,2,4]triazolo [4,3-b][1,2,4] benzotriazine derivative 14 which prepared by cyclocondensation of 1 b with ortho-aminothiophenol scheme (3).The structures of newly synthesized compounds were characterized by IR, 1 H NMR and mass spectral data.…”

“…[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 1 b with hydrazine hydrate followed by cyclocondensation with parachlorobenzaldehyde scheme (3). [1,2,4]triazolo [4,3-b][1,2,4] benzotriazine derivative 14 which prepared by cyclocondensation of 1 b with ortho-aminothiophenol scheme (3).The structures of newly synthesized compounds were characterized by IR, 1 H NMR and mass spectral data. Some of These compounds (7, 8 c , and 9 a ) were exhibited significant growth inhibition against (HepG2) cancer cell line when screened for their in vitro cytotoxic activity against human hepatocellular liver carcinoma (HepG2).…”