Synthesis of 5-substituted 1,3,4-thiadiazol-2-yl-sulfanylacetic acid derivatives

Abstract

The study is devoted to the design and synthesis of new 2,5-disubstituted 1,3,4-thiadiazoles 3a-k as a prom¬ising multi-targeted pharmacological scaffold. Heterocyclization of acylated thiosemicarbazides 1a-i with carbon disulfide lead to the intermediate 5-R-carbonylamino-1,3,4-thiadiazol-2-thioles 2a-i. Further S-al¬kylation of compounds 2a-i with chloroacetic acid amides and ethyl ester allowed to obtain the target 5-R-carbonylamino-1,3,4-thiadiazol-2-yl-sulfanylacetic acid derivatives 3a-k. The developed method could be used for producing of molecular diversity of disubstituted 5-amino-1,3,4-thiadiazol-2-thiols via variation of substituents on both functional groups. Synthesized compounds are discussed as prospective anticonvul¬sants and antiproliferative agents.