Affordable Access

deepdyve-link
Publisher Website

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.

Authors
  • Iikubo, Kazuhiko1
  • Kondoh, Yutaka1
  • Shimada, Itsuro1
  • Matsuya, Takahiro1
  • Mori, Kenichi1
  • Ueno, Yoko1
  • Okada, Minoru1
  • 1 Drug Discovery Research, Astellas Pharma Inc.
Type
Published Article
Journal
Chemical and Pharmaceutical Bulletin
Publisher
Pharmaceutical Society of Japan
Publication Date
Jan 01, 2018
Volume
66
Issue
3
Pages
251–262
Identifiers
DOI: 10.1248/cpb.c17-00784
PMID: 29491259
Source
Medline
Keywords
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times