Discovery of 3,5-diamino-1,2,4-triazole ureas as potent anaplastic lymphoma kinase inhibitors

Xianming Deng, Jinhua Wang, Jianming Zhang, Taebo Sim, Nam Doo Kim, Takaaki Sasaki, William Luther, Rani E. George, Pasi A. Jänne, Nathanael S. Gray

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC50 values of 70, 40, and 20 nM in Tel-ALK transformed Ba/F3 cells, respectively. Moreover, 15a and 23a potently inhibited the growth and survival of NPM-ALK positive anaplastic large cell lymphoma cell (SU-DHL-1) and neuroblastoma cell lines (KELLY, SH-SY5Y) containing the F1174L ALK mutation. These compounds provide novel leads for the development of small-molecule ALK inhibitors for cancer therapy.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume2
Issue number5
DOIs
Publication statusPublished - 2011 May 12

Keywords

  • 3,5-diamino-1,2,4-triazole urea
  • ALK

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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