Marsilje, Thomas, Pei, Wei, Lu, Wenshuo, Uno, Tetsuo, Jin, Yunho, Jiang, Tao, Kim, Sungjoon, Li, Nanxin, Sarkisova, Yelena, Steffy, Auzon, Culazzo, Annemarie, Kasibhatla, Shailaja, Joseph, Sean, Kim, Young, Tuntland, Tove, Cui, Xiaoming, Li, Jie, Gordon, William, Richmond, Wendy, Chang, Hsiao-Yen, Groessl, Todd, He, You-Qun, Liu, Bo, Fangxian, Sun, Phimister, Andrew, Aycinena, Juan, Bursulaya, Badry, Lee, Christian, Seidel, Martin, Harris, Jennifer and Michellys, Pierre (2013) Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro- N 2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)- N 4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. Journal of Medicinal Chemistry, 56 (14). pp. 5675-5690. ISSN 0022-2623

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 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients. © 2013 American Chemical Society.

Item Type:	Article
Date Deposited:	01 Dec 2017 00:45
Last Modified:	25 Jan 2019 00:46
URI:	https://oak.novartis.com/id/eprint/9239