Transformation of bis(2-chloroethyl)amino group into 1-piperazinyl in position 7 in the series of 6-nitroquinolonecarboxylic acid derivatives

Abstract

From the standpoint of designing new antibacterial preparations in the series of 6-fluoro-4-quinolone-3-carboxylic acid derivatives, piperazine radical is one of the most universal substituents for the position 7 featuring high antibacterial activity [I, 2]. A great majority of drugs belonging to this series have a residue of either piperazine itself (norfloxacin, ciprofloxacin, enofloxacin) or its derivative (lomefloxacin, pefloxacin, ofloxacin) in the seventh position of the cycle. A conventional method used for the synthesis of these compounds consists in condensation of a 7-halogen-substituted quinolonecarboxylic acid with an appropriate piperazine derivative. Previously we have established that, similar to the 6fluoroquinolone preparations, some derivatives of the 6-nitro-7-piperazinyl-4-quinolone-3-carboxylic acid possess significant antibacterial activity [3]. With a view to obtaining new 6-nitroquinolones, we have developed an alternative pathway for the synthesis of 7-piperazinyl-substituted quinolonecarboxylic acids. The key compounds in this method are 7-[bis(2-chloroethyl)amino]1-alkyl-6-nitro1,4-dihydro4-quinolinecarboxylic acids (IV) or their esters (I[I) readily obtained from the corresponding 7-chlorosubstituted derivatives (I) [4]. Interaction of compounds I with diethylamine" provides a high yield of 7-[bis(2-chloroethyl)amino]-substituted derivatives (II), which can be converted into III by treatment with thionyl chloride. The acid hydrolysis of III leads to acids IV. Heating acids IV with primary amines yields 7-(4-alkyll-piperazinyl)quinolinecarboxylic acids (V) that are hardly

DOI: 10.1007/BF02464281

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Cite this paper

@article{Glushkov2006TransformationOB, title={Transformation of bis(2-chloroethyl)amino group into 1-piperazinyl in position 7 in the series of 6-nitroquinolonecarboxylic acid derivatives}, author={R. G. Glushkov and Sergei A Zaitsev and I. B. Levshin and N. B. Marchenko}, journal={Pharmaceutical Chemistry Journal}, year={2006}, volume={31}, pages={609-611} }