Fluorinated 1,2,4-Triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives as antimycobacterial agents

Arch Pharm (Weinheim). 2009 Feb;342(2):94-9. doi: 10.1002/ardp.200800113.

Abstract

A series of fluorinated 1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives was designed and synthesized as fluoroquinolone analogues. The synthesized compounds were screened against Mycobacterium tuberculosis H(37)R(v) strain at 6.25 microg/mL concentration. Compound 4, the 7-oxo-2-(trifluoromethyl)-4,7-dihydro-1,2,4-triazolo[5,1-a]pyrimidine-6-carboxylic acid was found to be a very potent inhibitor, being able to inhibit 92% growth of M. tuberculosis H(37)R(v )at 6.25 microg/mL concentration. At the same time, it proofed to be nontoxic to mammalian cells (IC(50) > 62.5 microg/mL in VERO cells).

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / toxicity
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Fluoroquinolones / chemical synthesis*
  • Fluoroquinolones / chemistry
  • Fluoroquinolones / pharmacology
  • Fluoroquinolones / toxicity
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Pyrimidines / toxicity
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology
  • Triazoles / toxicity
  • Vero Cells

Substances

  • 7-oxo-2-(trifluoromethyl)-4,7-dihydro-1,2,4-triazolo(5,1-a)pyrimidine-6-carboxylic acid
  • Antitubercular Agents
  • Fluoroquinolones
  • Pyrimidines
  • Triazoles