Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials

Masahiro Taguchi, Hirosato Hondo, Yoshimasa Inoue, Yoshihiro Kawahata, Yoshikazu Jinbo, Fumio Sakamoto, Goro Tsukamoto

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 61 showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6I. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidine, morpholine, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 61 also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the car boxy group by a sulfonic acid group in 6I resulted in a complete loss of antibacterial activity.

Original languageEnglish
Pages (from-to)94-99
Number of pages6
JournalJournal of Medicinal Chemistry
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 1 1992
Externally publishedYes

Fingerprint

Quinolones
Gram-Negative Bacteria
Nalidixic Acid
Sulfonic Acids
Gram-Positive Bacteria
Sulfur
Seizures
Nitrogen
Carbon
Oxygen
Escherichia coli

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Taguchi, M., Hondo, H., Inoue, Y., Kawahata, Y., Jinbo, Y., Sakamoto, F., & Tsukamoto, G. (1992). Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials. Journal of Medicinal Chemistry, 35(1), 94-99. https://doi.org/10.1021/jm00079a011

Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials. / Taguchi, Masahiro; Hondo, Hirosato; Inoue, Yoshimasa; Kawahata, Yoshihiro; Jinbo, Yoshikazu; Sakamoto, Fumio; Tsukamoto, Goro.

In: Journal of Medicinal Chemistry, Vol. 35, No. 1, 01.01.1992, p. 94-99.

Research output: Contribution to journalArticle

Taguchi, M, Hondo, H, Inoue, Y, Kawahata, Y, Jinbo, Y, Sakamoto, F & Tsukamoto, G 1992, 'Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials', Journal of Medicinal Chemistry, vol. 35, no. 1, pp. 94-99. https://doi.org/10.1021/jm00079a011
Taguchi, Masahiro ; Hondo, Hirosato ; Inoue, Yoshimasa ; Kawahata, Yoshihiro ; Jinbo, Yoshikazu ; Sakamoto, Fumio ; Tsukamoto, Goro. / Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials. In: Journal of Medicinal Chemistry. 1992 ; Vol. 35, No. 1. pp. 94-99.
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