SYNTHESIS AND STUDY OF ANTIMICROBIAL ACTIVITY OF SOME PYRAZOLE-SUBSTITUTED 7H-[1,2,4]TRIAZOLO[3,4-B][1,3,4]THIADIAZINES
DOI:
https://doi.org/10.11603/2312-0967.2021.1.11986Keywords:
organic synthesis, NMR spectroscopy, 1-aryl-4-{3-aryl(getaryl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl)}-5-methyl-1H-pyrazole-3-carboxylates, antimicrobial activityAbstract
The aim of the work. To synthesize some new pyrazole-substituted 7H-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazines and to evaluate the antimicrobial properties of the obtained compounds.
Materials and Methods. Organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening.
Results and Discussion. As a result of ethyl-(2Z)-chloro (phenylhydrazone) acetates interaction with acetylacetone were obtained ethyl 4-acetyl-5-methyl-1-phenyl-1H-pyrazole-3-carboxylates. These compounds were subjected to bromination, which allowed to obtain the target bromoketones. The ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazole-3-carboxylates obtained at this stage were reacted with 4-amino-5-aryl (getaryl)-2,4-dihydro-3H-1,2,4-triazole-3-thions followed by formation of 1,3,4-thiadiazole ring and preparation of the corresponding ethyl 1-aryl-4-{3-aryl (getaryl)-7H-[1,2,4] triazolo [3,4-b][1,3,4] thiadiazin-6-yl)}-5-methyl-1H-pyrazole-3-carboxylates. The structures of the obtained compounds were confirmed by means of elemental analysis and NMR spectroscopy. In trems of the international project "The Community for Antimicrobial Drug Discovery" (CO-ADD), with the support of the Wellcome Trust (UK) and the University of Queensland (Australia), some synthesized compounds were screened for antimicrobial activity. Five bacterial strains were used as test microorganisms: Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603, Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 43300 and two strains of fungi: Candida albicans ATCC 90028 and Cryptococcus neoformans ATCC 208821. It was found that the studied compounds possess a variety of effects from almost complete absence to a pronounced antimicrobial effect.
Conclusions. Synthesis of 12 new ethyl 1-aryl-4-{3-aryl(getaryl)-7H-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazin-6-yl)}-5-methyl-1H-pyrazole-3-carboxylates was performed. These substances were obtained by reacting the corresponding ethyl 1-aryl-4- (bromoacetyl)-5-methyl-1H-pyrazole-3-carboxylates with 4-amino-5-aryl (getaryl)-2,4-dihydro-3H-1, 2,4-triazole-3-thions. Studies of the antimicrobial activity of the synthesized compounds demonstrated the potential for the discovery of antimicrobial agents among this class of compounds.
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