- Facile alkylation of 4-nitrobenzotriazole and its platelet aggregation inhibitory activity
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We explored the facile alkylation of 4-nitrobenzotriazole under basic conditions and the synthesized derivatives were tested for their potential ADP induced platelet aggregation inhibition activity in comparison with standard drug ticagrelor (selective P2Y12 inhibitor). The nitro group at 4-position is highly activating toward alkylation reactions (under strong basic conditions) and resulted in formation of degradation product like 3-nitrobenzene-1,2-diamine which make isolation of alkyl products very difficult. We optimized the reaction under mild basic condition (potassium carbonate and DMF) which is devoid of any degradation product. This is perhaps the first report of 4-nitrobenzotriazole derivatives possessing platelet aggregation inhibitory activity. Generally activity increases with increase in length of alkyl chain and 1-alkyl positional isomers were found to be more potent than 2-alkyl isomers. The benzoyl derivative was found to be the most potent [compound 22; (4-Nitro-1H-benzotriazol-1-yl)(phenyl)methanone; IC50 = 0.65 ± 0.10 mM] which may be attributed to electronegative oxygen atom and aromatic ring. Benzyl derivatives [compound 20; 1-Benzyl-4-nitro-1H-benzotriazole; IC50 = 0.81 ± 0.08 mM, compound 21; 2-Benzyl-4-nitro-2H-benzotriazole; IC50 = 0.82 ± 0.19 mM] and sulfonyl derivative [compound 23; 1-[(4-Methylphenyl)sulfonyl]-4-nitro-1H-benzotriazole; IC50 = 0.82 ± 0.19 mM] are also found to be highly active. Furthermore, all compounds possess P2Y12 binding affinity as confirmed by VASP/P2Y12 phosphorylation assay.
- Singh, Dhandeep,Silakari, Om
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- 1H, 13C and 15N NMR spectroscopy and tautomerism of nitrobenzotriazoles
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Benzotriazole nitro derivatives were prepared by nitration of the corresponding benzotriazoles and by methylation or cyclization of appropriate nitro-1,2-phenylenediamines. Structures and tautomerism of the nitrobenzotriazoles were studied by multinuclear 1H, 13C, 15N, and 2D NMR spectroscopy and quantum chemistry. Copyright
- Larina, Lyudmila I.,Milata, Viktor
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- [1,2,3]Triazolo[4,5-h]quinolones. A new class of potent antitubercular agents against multidrug resistant Mycobacterium tuberculosis strains
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In this preliminary study we report the activity of 3-methyl-9-substituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h]quinolone-carboxylic acids and their esters as a new class of antiinfective agents against MDR Mycobacterium tuberculosis. In antitubercular screening against H37Rv and 11 clinically isolated strains of M. tuberculosis several derivatives (1o,3a,c,i,j,p) showed MIC90 in the range 0.5-3.2 μg/mL. 3c showed no cytotoxicity and proved to be the most potent derivative exhibiting MIC90 = 0.5 μg/mL against all M. tuberculosis strains and infected human macrophages (J774-A1) tested.
- Carta, Antonio,Palomba, Michele,Paglietti, Giuseppe,Molicotti, Paola,Paglietti, Bianca,Cannas, Sara,Zanetti, Stefania
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p. 4791 - 4794
(2008/09/19)
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