Synthesis and biological activity of benzothiazolo[3,2-a]quinolone antibacterial agents

J Med Chem. 1986 Aug;29(8):1531-4. doi: 10.1021/jm00158a037.

Abstract

A new class of heterocyclic compounds with potent antibacterial activity, namely, 2-substituted amino-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3, 2-a]quinoline-6-carboxylic acids, is described. The compounds are conformationally restricted analogues of 7-substituted amino-6-fluoro-1-aryl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids. Compounds 7 and 10, having a 4-methylpiperazinyl and a piperazinyl substitution at the 2-position, respectively, possess in vitro antibacterial activities comparable to norfloxacin (15). Compound 8, which has a 4-acetylpiperazinyl substitution at the 2-position, is active against Gram-positive organisms and nearly inactive against Gram-negative organisms. An efficient and short synthesis of this novel heterocyclic system via an intramolecular nucleophilic displacement cyclization reaction is reported.

MeSH terms

  • Acinetobacter / drug effects
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Enterobacter / drug effects
  • Escherichia coli / drug effects
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology
  • Staphylococcus aureus / drug effects
  • Staphylococcus epidermidis / drug effects
  • Streptococcus / drug effects
  • Streptococcus pyogenes / drug effects
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology

Substances

  • Anti-Bacterial Agents
  • Quinolines
  • Thiazoles