Synthesis and pharmacological evaluation of N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide as cyclooxygenase inhibitors

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6745-9. doi: 10.1016/j.bmcl.2012.08.082. Epub 2012 Aug 31.

Abstract

A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular structures of two representative compounds, that is, 3 and 5l were confirmed by single crystal X-ray diffraction study. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. The compound 5i showed balanced selectivity towards COX-2 over COX-1 inhibition and good docking scores when docked into the COX-2 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Benzopyrans / chemistry*
  • Coumarins / chemistry
  • Coumarins / pharmacology
  • Crystallography, X-Ray
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Enzyme Activation / drug effects
  • Molecular Structure
  • Propane / chemistry*
  • Protein Binding / drug effects

Substances

  • Amides
  • Benzopyrans
  • Coumarins
  • Cyclooxygenase Inhibitors
  • coumarin
  • Propane