Synthesis of 3-heteryl substituted pyrrolidine-2,5-diones via catalytic Michael reaction and evaluation of their inhibitory activity against InhA and Mycobacterium tuberculosis

Eur J Med Chem. 2014 Jan:71:46-52. doi: 10.1016/j.ejmech.2013.10.069. Epub 2013 Nov 4.

Abstract

In the present paper, we report the synthesis via catalytic Michael reaction and biological results of a series of 3-heteryl substituted pyrrolidine-2,5-dione derivatives as moderate inhibitors against Mycobacterium tuberculosis H37Rv growth. Some of them present also inhibition activities against InhA.

Keywords: InhA; Michael addition; Succinimide; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Oxidoreductases / antagonists & inhibitors*
  • Oxidoreductases / metabolism
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacology*
  • Structure-Activity Relationship
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Pyrrolidines
  • Oxidoreductases
  • InhA protein, Mycobacterium
  • pyrrolidine