Discovery and optimization of 2-aryl oxazolo-pyrimidines as adenosine kinase inhibitors using liquid phase parallel synthesis

Bioorg Med Chem Lett. 2004 Apr 19;14(8):1997-2000. doi: 10.1016/j.bmcl.2004.01.082.

Abstract

Adenosine kinase inhibition is an attractive therapeutic approach for several conditions for example, neurodegeneration, seizures, ischemia, inflammation and pain. Several nucleosidic and non-nucleosidic inhibitors are available. Using a virtual screening approach, we have discovered that 2-aryl oxazolo-pyrimidines are adenosine kinase inhibitors. Subsequent high throughput derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives. A variety of analogues were produced by applying liquid phase parallel synthesis to vary the 7-amino residues as well as the 2-aryl moiety.

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors*
  • Adenosine Kinase / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*

Substances

  • Enzyme Inhibitors
  • Oxazoles
  • Pyrimidines
  • Adenosine Kinase