Synthesis, Spectral Characteristics, and Molecular Docking Studies of 2,4-Dichloro-<i>N</i>-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide

Abstract

Derivatives of 1,3,4-thiadiazole are of great interest for scientific and practical human activities as biologically active substances, dyes, components for creating semiconductors, energy accumulators, liquid crystals, polymers, nanomaterials, etc. Here we report the synthesis of 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide based on N,N’-disubstituted hydrazinecarbothioamide—2,4-dichloro-N-(2,2,2-trichloro-1-(2-(phenylcarbamothioyl)-hydrazine-1-carbothioamido)ethyl)benzamide. The method for obtaining the target product is based on the dehydrosulfurization reaction of the starting hydrazinecarbothioamide under the action of a mixture of iodine and triethylamine in a DMF medium. A new derivative of 1,3,4-thiadiazole was obtained in 84% yield, and its structure was confirmed by 1H and 13C NMR spectroscopy data. Molecular docking studies were carried out with the structure of the resulting compound and dihydrofolate reductase (DHFR) in the AutoDock Vina program. The resulting compound is a potential inhibitor of DHFR and surpasses several known analogues in terms of the strength of the complex formed with the active site of this enzyme.

Keywords

• synthesis
• 1,3,4-thiadiazole
• dehydrosulfurization
• dihydrofolate reductase
• molecular docking