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

Abstract

A series of novel 7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid derivatives was synthesized in good yields by a multi-step procedure that included the generation of the S-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 1H-NMR, 13C-NMR and HRMS spectra. The intramolecular cyclization occurred regioselectively at the N2-position of 1,2,4-triazine ring, which was confirmed by compound 3e using single-crystal X-ray diffraction analysis. The antibacterial and antitubercular activities of the target compounds were evaluated. Compared with Ciprofloxacin and Rifampicin, compounds 5d, 5f and 5g 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 5f also displayed excellent in vitro antitubercular activity against Mycobacterium smegmatis (minimum inhibitory concentration (MIC) = 50 μg/mL) and better growth inhibition activity of leucyl-tRNA synthetase (78.24 ± 4.05% at 15 μg/mL).

Green electro-organic synthesis of a novel catechol derivative based on o-benzoquinone nucleophilic addition

“…The proton NMR spectrum of adduct 9 (Fig. 8) showed accompanying broad bands at chemical shift ( δ 5.93–6.03 ppm) could be assigned to two NH protons 23,52–56 of the novel triazinone ring. Similarly, 2 accompanied OH protons exist as a broad peak at chemical shift ( δ 7.50 ppm) formed merged with a third amidic NH proton at δ 7.80 ppm.…”

“…On the other hand, the appearance of only two sharp bands of the aromatic protons at chemical shifts δ 6.73 ppm (dd, J = 5.7, 3.6 Hz, 1 H) and δ 6.57 ppm (dd, J = 5.7, 3.6 Hz, 1 H) confirmed without any doubt the formation of the novel triazinone ring in conjugation with the catechol ring. 11,53 These two aromatic protons appear as double doublets due to the long-range coupling between OH and NH groups. However, 1 H NMR in D 2 O, the exchangeable protons (OH and NH) disappear, 23,52–55 and the aromatic protons of triazinone product 9 show two singlet peaks at chemical shifts δ 7.00 ppm and δ 7.07 ppm as shown in the ESI† (Fig.…”

“…11,53 These two aromatic protons appear as double doublets due to the long-range coupling between OH and NH groups. However, 1 H NMR in D 2 O, the exchangeable protons (OH and NH) disappear, 23,52–55 and the aromatic protons of triazinone product 9 show two singlet peaks at chemical shifts δ 7.00 ppm and δ 7.07 ppm as shown in the ESI† (Fig. S1).…”

The Riveting Chemistry of Poly‐aza‐heterocycles Employing Microwave Technique: A Decade Review

“…The protocol was employed to prepare potent antibacterial and antitubercular agents in a multi‐step synthesis (Scheme 23). [31] …”

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

“…A significant number of biologically active thiazolidines amount to their heteroannelated derivatives, namely, condensed thiazolo [3,2-a]pyrimidines [9] and thiazolo [3,2-b]-1,2,4-triazoles [10], as well as related thiazolo [3,2-b]-1,2,4-triazines and thiazolo [2,3-c]-1,2,4-triazines possessing antimicrobial, antidepressant, anti-HIV, and anticancer activities [10][11][12][13][14][15]. Modifications of the position 5 of the thiazolidine cycle often lead to an enhancement of the pharmacological properties of the resulting products, which have received considerable attention in reviews [16,17].…”