Novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent c-Met/ALK multikinase inhibitory activities

Zhiqing Liu, Jing Ai, Xia Peng, Zilan Song, Kui Wu, Jing Zhang, Qizheng Yao, Yi Chen, Yinchun Ji, Yanhong Yang, Meiyu Geng, Ao Zhang

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

Original languageEnglish (US)
Pages (from-to)304-308
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume5
Issue number4
DOIs
StatePublished - Apr 10 2014

Keywords

  • 2,4-diarylaminopyrimidine analogues
  • C1-Substituted- N 3-benzazepine
  • c-Met/ALK dual inhibitor
  • structure repurposing

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Liu, Z., Ai, J., Peng, X., Song, Z., Wu, K., Zhang, J., Yao, Q., Chen, Y., Ji, Y., Yang, Y., Geng, M., & Zhang, A. (2014). Novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent c-Met/ALK multikinase inhibitory activities. ACS Medicinal Chemistry Letters, 5(4), 304-308. https://doi.org/10.1021/ml400373j