Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential inhibitors of chorismate mutase

Bioorg Chem. 2013 Dec:51:48-53. doi: 10.1016/j.bioorg.2013.08.002. Epub 2013 Aug 19.

Abstract

A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30μM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76±0.54μM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM.

Keywords: Alkyne; Chorismate mutase; Iodine; Palladium; Pyrimidinone.

MeSH terms

  • Alkynes / chemistry*
  • Chorismate Mutase / antagonists & inhibitors*
  • Chorismate Mutase / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Mycobacterium tuberculosis / enzymology
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • 3,4-dihydropyridopyrimidin-2(1H)-one
  • Alkynes
  • Enzyme Inhibitors
  • Pyrimidinones
  • Chorismate Mutase