Furo[2,3‐d]pyrimidines and Oxazolo[5,4‐d]pyrimidines as Inhibitors of Receptor Tyrosine Kinases (RTK)

Abstract

AbstractReceptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4‐d]pyrimidines and furo[2,3‐d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC50 values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p, and 20r, had an IC50 of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.