Optimization of 6, 7-disubstituted-4-(arylamino) quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase …

…, EG Overbeek-Klumpers, WA Hallett…

Index: Tsou, Hwei-Ru; Overbeek-Klumpers, Elsebe G.; Hallett, William A.; Reich, Marvin F.; Floyd, M. Brawner; Johnson, Bernard D.; Michalak, Ronald S.; Nilakantan, Ramaswamy; Discafani, Carolyn; Golas, Jonathan; Rabindran, Sridhar K.; Shen, Ru; Shi, Xiaoqing; Wang, Yu-Fen; Upeslacis, Janis; Wissner, Allan Journal of Medicinal Chemistry, 2005 , vol. 48, # 4 p. 1107 - 1131

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Citation Number: 196

Abstract

A series of new 6, 7-disubstituted-4-(arylamino) quinoline-3-carbonitrile derivatives that function as irreversible inhibitors of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) kinases have been prepared. These compounds demonstrated enhanced activities for inhibiting HER-2 kinase and the growth of HER-2 positive cells compared to our EGFR kinase inhibitor 86 (EKB-569). Three synthetic routes ...