Design, synthesis, and properties of (4S)-7-(4-amino-2-substituted-pyrrolidin-1-yl)quinolone-3-carboxyl ic acids

The quinolonecarboxylic acids are potent and orally active broad-spectrum antibacterial agents. These compounds inhibit DNA gyrase, a key enzyme in bacterial DNA replication. The 7-(3-aminopyrrolidiny)quinolone A-60969 is particularly potent and is undergoing clinical evaluation. The authors studied...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-01, Vol.31 (8), p.1598-1611
Main Authors: Rosen, T, Chu, DTW, Lico, I M, Fernandes, P B, Marsh, K, Shen, L, Cepa, V G, Pernet, A G
Format: Article
Language:English
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Summary:The quinolonecarboxylic acids are potent and orally active broad-spectrum antibacterial agents. These compounds inhibit DNA gyrase, a key enzyme in bacterial DNA replication. The 7-(3-aminopyrrolidiny)quinolone A-60969 is particularly potent and is undergoing clinical evaluation. The authors studied a series of enantiomerically homogeneous (4S)-7-(4-amino-2-substituted-pyrrolidinyl)quinolones in an effort to utilize the 2-position of the pyrrolidine moiety to improve upon the solubility and pharmacokinetic properties of this class of compounds while maintaining potent antibacterial activity. They found that the absolute stereochemistry at the 2-position of the pyrrolidine ring is critical to the maintenance of such activity. They report the full details of the asymmetric synthesis and the in vitro and in vivo structure-activity relationships of this series of compounds as well as the physiochemical properties.
ISSN:0022-2623