Derivatives of 1,3,4-thiadiazole are of great interest to medicine and pharmacy as potential drug substances. Recently, a large number of works have appeared on the inhibition of dihydrofolate reductase (DHFR) by representatives of this class of compounds, which makes them promising antitumor agents. In this work, we carried out molecular docking studies of amidoalkyl derivatives of 1,3,4-thiadiazole - N-(2,2,2-trichloro-1-((5-aryl-1,3,4-thiadiazol-2-yl)amino)ethyl)carboxamides and N-(2,2,2-trichloro-1-((5-(arylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)carboxamides with DHFR. The AutoDock Vina program based on the PyRx 0.8 platform was used for docking. Before docking, the enzyme structure (PDB ID: 1DLS) was prepared using the Chimera 1.14 program, and the structures of potential inhibitors and reference preparations were optimized by the PM3 method in the ArgusLab 4.0.1 program. According to the results of molecular docking, the analyzed compounds effectively interact with the active site of DHFR. It is shown that the introduction of an NH group between the 1,3,4-thiadiazole and aromatic rings leads to stronger binding of ligands to DHFR. Based on the results of molecular docking, hit compounds were selected - 4-methyl-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide and 4-methyl-N-(2,2,2-trichloro-1-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide, which are superior to the reference compounds according to the strength of the formed complex.