Antimicrobials are an important class of agents because they prevent many deaths caused by bacterial infections, which nevertheless remain one of the leading causes of death worldwide. The main problem with antimicrobial therapy is the appearance of resistant strains of bacteria. The reason for their formation is the incorrect use of antibiotics, and the big problem is also that fewer new active agents are coming to the market. According to the mechanism of action, we know several groups of agents and one of the important targets of antimicrobial agents is gyrase B. As part of the experimental work, we will synthesize new inhibitors that work by competing for the binding site with ATP.
We prepared inhibitors with a benzothiazole frame, on which 3,4-dichloro-5-methylpyrrole was attached to position 2, where the amine functional group is located, and an ethanamine spacer was attached to the amide or phenolic functional group. When evaluating synthesis results various analytical techniques were used, such as liquid chromatography coupled with a mass spectrometer and thin-layer chromatography. The structure was finally confirmed with nuclear magnetic resonance. The originally planned synthesis route via N-alkylation of benzothiazole did not give the desired compound, so we searched for suitable alternatives. As appropriate was nucleophilic aromatic substitution with Boc-protected ethylenediamine and p-fluoronitrobenzene. This was followed by acetylation, reduction of the nitro group and cyclization to the desired product. In the end, we successfully isolated only one final compound.
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