Synthesis and Antibacterial Activity of a New Series of Tetracyclic Pyridone Carboxylic Acids. 2

Yoshikazu Jinbo, Masahiro Taguchi, Yoshimasa Inoue, Hirosato Kondo, Tomohiro Miyasaka, Hideki Tsujishita, Fumio Sakamoto, Goro Tsukamoto

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A novel tetracyclic pyridone carboxylic acid with a thiazolidine ring, 1,2-dihydro-9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid (4a), and variants with a nitrogen atom (4b) or carbonyl group (4c) in the place of the 10-position oxygen atom of 4a were prepared and tested for antibacterial activity and inhibitory activity on DNA gyrase from Escherichia coli KL-16. The in vitro antibacterial potency with regard to the 10-position atom was found to be of the following order; O > NCH3 = C═O. The IC50 values for DNA gyrase inhibition activity for the 4a, 4b, and 4c compounds were 0.33, 0.53, and 0.67 g/mL, respectively. The activity of 4a, in which the C-3 methyl group and C-5 of ofloxacin (2a) were connected with a sulfur atom to restrict the conformation of 2a, was more potent than that of 2a against both Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa. Compared to the tetracyclic pyridone carboxylic acid la, which has a flat thiazole ring, compound 4a showed comparable or slightly more potent activity against both Gram-positive and -negative bacteria, except for P. aeruginosa.

Original languageEnglish
Pages (from-to)3148-3153
Number of pages6
JournalJournal of Medicinal Chemistry
Issue number21
Publication statusPublished - Jan 1 1993
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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