Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors.
Buchanan J.L., Newcomb J.R., Carney D.P., Chaffee S.C., Chai L., Cupples R., Epstein L.F., Gallant P., Gu Y., Harmange J.C., Hodge K., Houk B.E., Huang X., Jona J., Joseph S., Jun H.T., Kumar R., Li C., Lu J., Menges T., Morrison M.J., Novak P.M., van der Plas S., Radinsky R., Rose P.E., Sawant S., Sun J.R., Surapaneni S., Turci S.M., Xu K., Yanez E., Zhao H., Zhu X.
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.
Bioorg. Med. Chem. Lett. 21:2394-2399(2011) [PubMed] [Europe PMC]