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

✍ Scribed by Andreas Martin-Kohler; Jörg Widmer; Guido Bold; Thomas Meyer; Urs Séquin; Peter Traxler

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 276 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490089

✦ Synopsis

Abstract

Receptor 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 IC~50~ 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 IC~50~ of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.