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

Yoshikazu Jinbo, Hirosato Kondo, Yoshimasa Inoue, Masahiro Taguchi, Hideki Tsujishita, Yasuo Kotera, Fumio Sakamoto, Goro Tsukamoto

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,l-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E. coli KL-16. The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe ≥ O > S ≫ CO. Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity. 7-Fluoro-9,1-[(N-methylimino)methano]-8-(4-methyl-1-piperazinyl)-5-oxo-5ff-thiazolo[3,2-a]quinoline-4-carboxylic acid (10-NCH3) showed potent in vivo antibacterial activity.

Original languageEnglish
Pages (from-to)2621-2626
Number of pages6
JournalJournal of Medicinal Chemistry
Volume36
Issue number18
DOIs
Publication statusPublished - Jan 1 1993
Externally publishedYes

Fingerprint

DNA Gyrase
Pyridones
Carboxylic Acids
Carbon Monoxide
Sulfur
Nitrogen
Oxygen
Escherichia coli
quinoline-4-carboxylic acid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and Antibacterial Activity of a New Series of Tetracyclic Pyridone Carboxylic Acids. / Jinbo, Yoshikazu; Kondo, Hirosato; Inoue, Yoshimasa; Taguchi, Masahiro; Tsujishita, Hideki; Kotera, Yasuo; Sakamoto, Fumio; Tsukamoto, Goro.

In: Journal of Medicinal Chemistry, Vol. 36, No. 18, 01.01.1993, p. 2621-2626.

Research output: Contribution to journalArticle

Jinbo, Y, Kondo, H, Inoue, Y, Taguchi, M, Tsujishita, H, Kotera, Y, Sakamoto, F & Tsukamoto, G 1993, 'Synthesis and Antibacterial Activity of a New Series of Tetracyclic Pyridone Carboxylic Acids', Journal of Medicinal Chemistry, vol. 36, no. 18, pp. 2621-2626. https://doi.org/10.1021/jm00070a005
Jinbo, Yoshikazu ; Kondo, Hirosato ; Inoue, Yoshimasa ; Taguchi, Masahiro ; Tsujishita, Hideki ; Kotera, Yasuo ; Sakamoto, Fumio ; Tsukamoto, Goro. / Synthesis and Antibacterial Activity of a New Series of Tetracyclic Pyridone Carboxylic Acids. In: Journal of Medicinal Chemistry. 1993 ; Vol. 36, No. 18. pp. 2621-2626.
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