Triazolo[3,4-b][1,3,4]thiadiazole molecules are found to be important tools in modern bioorganic and medicinal chemistry. This condensed system successfully combines two pharmacologically significant five-membered heterocycles – 1,2,4-triazole and 1,3,4-thiadiazole, which causes much more interest in the enhanced activity profile of its analogs than their parent separate constituents. It’s considered that the triazoles fused to thiadiazoles exhibit various therapeutically important properties, probably due to the existence of N-C-S fragments in their structures. In this review, we presented the summarized literature data about the diversity of pharmacological effects of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole based compounds as promising objects for the rational design of drug-like molecules.

Triazolo[3,4-b]thiadiazoles are a class of heterocyclic compounds, which have attracted great interest in medicinal chemistry owing to their wide range of pharmacological activities. A number of triazoles fused to thiadiazoles are incorporated into a wide variety of therapeutically important compounds possessing a broad spectrum of biological activities. Considering such a significant pharmacological potential, as well as wide synthetic possibilities triazolo-thiadiazoles have received considerable attention from scientific community and are extensively used for construction of prospective drug-likes molecules. In this review, we summarized the literature data about the main synthetic approaches for obtaining condensed heterocyclic compounds based on triazolo[3,4-b][1,3,4]thiadiazole scaffold as promising objects for modern bioorganic and medicinal chemistry.

A novel 1,3,4-thiadiazole containing 2-iminothiazolidine-4-ones 4a-b were synthesized through the reaction of 2-chloro-N-(5-ethyl/allylsulfanyl-[1,3,4]thiadiazol-2-yl)-acetamides 1a-b with ammonium thiocyanate in dry acetone. Condensation of 4a-b with various carbonyl compounds according to the standard Knoevenagel procedure yielded the corresponding 5-arylidene- (5a-d), 5-heterylidene- (6a-c), 5-isatinylidene- (7a-b) and 5-(3-phenyl-2-propene-1-ylidene)- (8a-b) derivatives. All the newly synthesized compounds were confirmed by their elemental analysis and spectral data. Synthesized compounds 4a, 5a, 5b, 6a, 6c and 7a were screened for their in vitro antitrypanosomal activity against T. brucei gambience (Feo strain). The 5-ylidene substituted compounds with S-allyl group in position 5 of thiadiazole cycle (5a, 5b, 6a and 7a) displayed good to excellent antitrypanosomal potency with a range IC50 = 7.3-12.8 µM.