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

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.

• Authors: M Bauser, G Delapierre, M Hauswald, T Flessner, D D'Urso, A Hermann, B Beyreuther, J De Vry, P Spreyer, E Reissmüller, H Meier
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 8 Pg. 1997-2000 (Apr 19 2004) ISSN: 0960-894X [Print] England
• PMID: 15050645 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Oxazoles
• Pyrimidines
• Adenosine Kinase

Topics

• Adenosine Kinase (antagonists & inhibitors, metabolism)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Oxazoles (chemical synthesis, chemistry)
• Pyrimidines (chemical synthesis, pharmacology)