2-Heteroaryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6 H)-thiones and Their S-Substituted Derivatives: Synthesis, Spectroscopic Data, and Biological Activity.

In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2-heteroaryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6 H)-thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2-(3-heteroaryl-[1,2,4]triazol-5-yl)phenyl]amines with carbon disulfide, potassium ethyl xanthogenate, or aryl isothiocyanates, and in situ reaction of 2-isothiocyanatobenzonitrile with hydrazides. A series of N-R-2-[(2-heteroaryl-[1,2,4]triazole-[1,5-c]quinazoline-5-yl)thio]acetamides were obtained by aminolysis of the corresponding acetic acids and alkylation of potassium thiolates with N-R-2-chloroacetamides. It was established that some potassium thiolates, 4 a-4 d, 4 h, and 4 i, had high antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration of 12.5 μg mL-1 and minimum bactericidal concentration of 25 μg mL-1 , which exceeded the values for trimethoprim. In addition, {2-[3-(1 H-indole-2-yl)-1 H-1,2,4-triazol-5-yl]phenyl}amine 2 i was investigated in the concentration range 100-0.01 μM at 59 lines of nine cancer cell types, and showed a mean effective concentration at 3.12-7.03 μM and cytotoxic effect at 15.56-67.38 μM. The possible mechanisms of activity were predicted by molecular docking studies to S. aureus dihydrofolate reductase and epidermal growth factor receptor kinase.