Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 ��M, respectively) and turned out to be a selective and potent CRAF inhibitor. �� 2010 Elsevier Ltd. All rights reserved.This research was supported by Korea Institute of Science and Technology (KIST) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0087992 ; J.M.H.). We also thank Dr. Merlyn lab at Wistar Institute for the kind supply of WM3629 cell line