Details

Autor(en) / Beteiligte

• 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

Titel

Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5‑Chloro‑N2‑(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)‑N4‑(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

Ist Teil von

• Journal of medicinal chemistry, 2013-07, Vol.56 (14), p.5675-5690

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.