Synthesis of 2-Amino-5-sulfanyl-1,3,4-thiadiazole Derivatives as Anticonvulsant Agents

Background:1,3,4-thiadiazoles are associated with diverse biocidal activities. A large number of 1,3,4-thiadiazoles have been reported as anticancer, antitubercular, antiflammatory, and pesticide agents. This compounds possessed potent anticonvulsant activity in wide range preclinical in vitro and in vivo models. Material and methods: The study is devoted to the design and synthesis of new 2,5-disubstituted 1,3,4-thiadiazoles 3a-d as a promising muilt-targeting pharmacological scaffold. Heterocyclization of thiosemicarbazide 1 with carbon disulfide lead to the intermediate 5-amino-1,3,4-thiadiazole-2-thiole 2. Further S-alkylation of compound 2 with halo-acetophenone allowed to abtain the target 2-((5-amino-1,3,4-thiadiazol-2-yl) thio)-1-phenylethan-1-one derivatives 3a-d. The reduction of compounds with sodium borohydride was studied and resulted in 4a-d compounds. Results: The structures of these compounds were stablished by means of 1HNMR. Conclusions: The SAR study of synthesized compounds reveals that halo-acetophenone attached to 1,3,4-thiadiazole ring as substituent linked to sulfonyl group could be studied for anticonvulsant efficacy. Additionally, anticonvulsant activity of carbonyl compounds could be compared to hydroxyl-containing structures.

Keywords:

1 , 3 , 4-thiadiazole , anticonvulsant , synthesis , 1HNMR