Synthesis and Investigation of Phthalazinones as Antitubercular Agents

Chem Asian J. 2019 Apr 15;14(8):1278-1285. doi: 10.1002/asia.201801805. Epub 2019 Feb 13.


A series of 2- and 7-substituted phthalazinones was synthesised and their potential as anti-tubercular drugs assessed via Mycobacterium tuberculosis (mc2 6230) growth inhibition assays. All phthalazinones tested showed growth inhibitory activity (MIC <100 μm), and those compounds containing lipophilic and electron-withdrawing groups generally exhibited better anti-tubercular activity. Several lead compounds were identified, including 7-((2-amino-6-(4-fluorophenyl)pyrimidin-4-yl)amino)-2-heptylphthalazin-1(2H)-one (MIC=1.6 μm), 4-tertbutylphthalazin-2(1H)-one (MIC=3 μm), and 7-nitro-phthalazin-1(2H)-one (MIC=3 μm). Mode of action studies indicated that selected pyrimidinyl-phthalazinones may interfere with NADH oxidation, however, the mode of action of the lead compound is independent of this enzyme. MIC=minimum inhibitory concentration.

Keywords: Medicinal Chemistry; Nitrogen Heterocycles; Phthalazinones; Tuberculosis.

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Phthalazines / chemical synthesis*
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Structure-Activity Relationship


  • Antitubercular Agents
  • Phthalazines