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

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. The discovery of oxazolo-pyrimidines as structurally novel adenosine kinase inhibitors is presented. High throughput derivatization of the oxazolo-pyrimidine scaffold was performed using liquid phase parallel synthesis techniques. This led to the discovery of the title compound, an adenosine kinase inhibitor with a≤10 nanomolar IC 50 value.