Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors

The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the regulation of cell growth and differentiation, and in protection from apoptosis. IGF-1R has been shown to be an appealing target for the treatment of human cancer. Herein, we report the synthesis, structure–activity relationships (SAR), X-ray cocrystal structure and in vivo tumor study results for a series of 2,4-bis-arylamino-1,3-pyrimidines.

Graphical abstractThe discovery of 2,4-bis-arylamino-1,3-pyrimidines as IGF-1R inhibitors is described. Optimization studies led to the identification of 26, which displayed tumor growth inhibition in a mouse Calu-6 tumor xenograft study.Figure optionsDownload full-size imageDownload as PowerPoint slide