Discovery of N-{2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N′-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor

Kazuhiko Iikubo; Yutaka Kondoh; Itsuro Shimada; Takahiro Matsuya; Kenichi Mori; Yoko Ueno; Minoru Okada

doi:10.1248/cpb.c17-00784

Current Topics: Regular Articles

Discovery of N-{2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N′-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor

Kazuhiko Iikubo , Yutaka Kondoh, Itsuro Shimada, Takahiro Matsuya, Kenichi Mori, Yoko Ueno, Minoru Okada

著者情報

キーワード: 1,3,5-triazine, non-small cell lung cancer, anaplastic lymphoma kinase, echinoderm microtubule-associated protein-like 4

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2018 年 66 巻 3 号 p. 251-262

DOI https://doi.org/10.1248/cpb.c17-00784

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抄録

Anaplastic lymphoma kinase (ALK) is a validated therapeutic target for treating echinoderm microtubule-associated protein-like 4 (EML4)-ALK positive non-small cell lung cancer (NSCLC). We synthesized a series of 1,3,5-triazine derivatives and identified ASP3026 (14a) as a potent and selective ALK inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, once-daily oral administration of 14a demonstrated dose-dependent antitumor activity. Here, syntheses and structure–activity relationship (SAR) studies of 1,3,5-triazine derivatives are described.

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