Synthesis, Characterization, and Biological Evaluation of Novel 7-Oxo-7-thiazolo[3,2-]-1,2,4-triazine-2-carboxylic Acid Derivatives.

A series of novel 7-oxo-7-thiazolo[3,2-]-1,2,4-triazine-2-carboxylic acid derivatives was synthesized in good yields by a multi-step procedure that included the generation of the -alkylated derivatives from 6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones with ethyl 2-chloroacetoacetate, intramolecular cyclization with microwave irradiation, hydrolysis and amidation. All of the target compounds were fully characterized through H-NMR, C-NMR and HRMS spectra. The intramolecular cyclization occurred regioselectively at the 2-position of 1,2,4-triazine ring, which was confirmed by compound using single-crystal X-ray diffraction analysis. The antibacterial and antitubercular activities of the target compounds were evaluated. Compared with Ciprofloxacin and Rifampicin, compounds , and containing the terminal amide fragment exhibited broad spectrum antibacterial activity, and carboxylic acid derivatives or its corresponding ethyl esters had less effect on antibacterial properties. The most potent compound also displayed excellent in vitro antitubercular activity against (minimum inhibitory concentration (MIC) = 50 μg/mL) and better growth inhibition activity of leucyl-tRNA synthetase (78.24 ± 4.05% at 15 μg/mL).