Synthesis, structure–activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-Chloro-N 2-(2- …

…, M Warmuth, Y Sarkisova, F Sun, A Steffy…

Index: Marsilje, Thomas H.; Pei, Wei; Chen, Bei; Lu, Wenshuo; Uno, Tetsuo; Jin, Yunho; Jiang, Tao; Kim, Sungjoon; Li, Nanxin; Warmuth, Markus; Sarkisova, Yelena; Sun, Frank; Steffy, Auzon; Pferdekamper, Annemarie C.; Li, Allen G.; Joseph, Sean B.; Kim, Young; Liu, Bo; Tuntland, Tove; Cui, Xiaoming; Gray, Nathanael S.; Steensma, Ruo; Wan, Yongqin; Jiang, Jiqing; Chopiuk, Greg; Li, Jie; Gordon, W. Perry; Richmond, Wendy; Johnson, Kevin; Chang, Jonathan; Groessl, Todd; He, You-Qun; Phimister, Andrew; Aycinena, Alex; Lee, Christian C.; Bursulaya, Badry; Karanewsky, Donald S.; Seidel, H. Martin; Harris, Jennifer L.; Michellys, Pierre-Yves Journal of Medicinal Chemistry, 2013 , vol. 56, # 14 p. 5675 - 5690

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Citation Number: 146

Abstract

The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure–activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 ...