Synthesis and Antibacterial Activity of Thiazolopyrazine-Incorporated Tetracyclic Quinolone Antibacterials

Yoshimasa Inoue, Hirosato Kondo, Masahiro Taguchi, Yoshikazu Jinbo, Fumio Sakamoto, Goro Tsukamoto

研究成果: Contribution to journalArticle査読

27 被引用数 (Scopus)

抄録

A novel series of 8-substituted-9,1-[(N-methylimino)methano]-7-fluoro-5-oxo-5H-thiazolo[3,2-a]-quinoline-4-carboxylic acids 5a-q having a unique thiazolopyrazine-incorporated tetracyclic structure were synthesized, and the in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. All compounds 5a-q had more potent activity than ofloxacin (6), which is one of the most popular quinolones, against Gram-positive and Gram-negative bacteria. The 8-pyrrolidinyl, 5a-e, and 8-morpholino, 5p, derivatives showed the most potent activity against Gram-positive bacteria. It is also significant that these compounds, 5a-q, showed more potent antibacterial activity against methicillin-resistant Staphylococcus aureus isolates (MRSA) than ofloxacin (6). The combination of the morpholino group and this unique tetracyclic thiazolopyrazine skeleton contributes to the enhancement of the antibacterial activity against MRSA isolates. The in vivo antibacterial activities of these compounds, 5a-q, were limited and depended on the structure of the 8-substituent. The 8-(4-alkyl-1-piperazinyl) derivatives 5g, 5h, 5j, and 5n provided good oral efficacy and exhibited more potent activity than ofloxacin (6) against the systematic infection with S. aureus IID 803 in mice.

本文言語英語
ページ(範囲)586-592
ページ数7
ジャーナルJournal of Medicinal Chemistry
37
5
DOI
出版ステータス出版済み - 3 1 1994
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

フィンガープリント 「Synthesis and Antibacterial Activity of Thiazolopyrazine-Incorporated Tetracyclic Quinolone Antibacterials」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル