Discovery of novel antitubercular 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5259-61. doi: 10.1016/j.bmcl.2011.07.035. Epub 2011 Jul 19.

Abstract

In the present investigation, a series of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed low to high inhibitory activities against Mycobacterium tuberculosis H(37)Rv and INH resistant M. tuberculosis. The compound 3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (4o) was found to be the most promising compound active against M. tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentration 3.12 μM and 6.25 μM, respectively.

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Chlorocebus aethiops
  • Drug Discovery*
  • Indenes / chemical synthesis
  • Indenes / chemistry
  • Indenes / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thioamides / chemical synthesis
  • Thioamides / chemistry
  • Thioamides / pharmacology*
  • Vero Cells

Substances

  • 3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno(1,2-c)pyrazole-2-carbothioamide
  • Antitubercular Agents
  • Indenes
  • Pyrazoles
  • Thioamides