Pyrazole and imidazo[1,2-b]pyrazole Derivatives as New Potential Antituberculosis Agents

Med Chem. 2019;15(1):17-27. doi: 10.2174/1573406414666180524084023.

Abstract

Background: We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening showed that many compounds are able to totally inhibit Mycobacterium growth (>90 %). Among the most active compounds, we selected some new possible hits based on their similarities and, at the same time, on their novelty with respect to the pipeline drugs.

Methods: In order to increase the potency and obtain more information about structure-activity relationship (SAR), we designed and synthesized three new series of compounds (2a-e, 3a-e, and 4a-l).

Conclusion: Performed tests confirmed that both new pyrazoles and imidazo-pyrazoles could represent a new starting point to obtain more potent compounds and further work is now underway to identify the protein targets of this new class of anti-TB agents.

Keywords: LORA; MABA; Pyrazole; Tuberculosis (TB); antitubercular agents; imidazo[1,2-b]pyrazole..

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / toxicity
  • Chlorocebus aethiops
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Imidazoles / toxicity
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrazoles / toxicity
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antitubercular Agents
  • Imidazoles
  • Pyrazoles
  • Small Molecule Libraries