A series of novel 1,3,4-thia(oxa)diazole substituted 2-(2,4-dioxothiazolidine-5-ylidene)-acetamides 3a-c, 4 and 5a-k have been synthesized following the acylation reaction of 2-amino-5-aryl-1,3,4-oxadiazoles, 5-amino-1,3,4-thiadiazole-2-thiol and it’s S-alkylated derivatives with 2-(2,4-dioxothiazolidine-5-ylidene)acetyl chloride in dioxane medium. The functionalization of compounds 3b, 3c, 5d and 5e was carried out on their N3 position under N-alkylation conditions with N-aryl-2-chloroacetamides in DMF/ethanol medium yielded the corresponding 2,4-dioxothiazolidine-3,5-diacetic acid diamides 6a-e and 7a-b. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. The antioxidant activity evaluation in vitro of the synthesized compounds was performed by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the highly active compound 4, namely 2-(2,4-dioxothiazolidin-5-ylidene)-N-(5-mercapto-[1,3,4]thiadiazol-2-yl)acetamide was found to be the most efficient candidate among all compounds with a radical scavenging ability of 88.9%, which was comparable that for ascorbic acid (92.7%). The experimentally calculated IC50 value of 43.1 μM for compound 4 was lower than for ascorbic acid (50.5 μM).

Condensed bicyclic systems with thiadiazole core being annelated to other five-membered heterocycles such as 1,3-thiazole, imidazole or 1,2,4-triazole occupy prominent place in medicinal chemistry because of their broad spectrum of pharmacological activities. The combination of several heterocycles into a bicyclic system commonly provides much more interest in the enhanced activity profile of its analogs than their parent separate constituents. In this review, we summarized the literature data about the main approaches for obtaining and possible directions of structural modification of the most common 1,3,4-thiadiazole containing [5+5] annelated heterosystems as promising objects for modern medicinal chemistry.