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

…, L Chai, R Cupples, LF Epstein, P Gallant, Y Gu…

Index: Buchanan, John L.; Newcomb, John R.; Carney, David P.; Chaffee, Stuart C.; Chai, Lilly; Cupples, Rod; Epstein, Linda F.; Gallant, Paul; Gu, Yan; Harmange, Jean-Christophe; Hodge, Kathy; Houk, Brett E.; Huang, Xin; Jona, Janan; Joseph, Smriti; Jun, H. Toni; Kumar, Rakesh; Li, Chun; Lu, John; Menges, Tom; Morrison, Michael J.; Novak, Perry M.; Van Der Plas, Simon; Radinsky, Robert; Rose, Paul E.; Sawant, Satin; Sun, Ji-Rong; Surapaneni, Sekhar; Turci, Susan M.; Xu, Keyang; Yanez, Evelyn; Zhao, Huilin; Zhu, Xiaotian Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 8 p. 2394 - 2399

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Citation Number: 14

Abstract

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.