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

23 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Dopamine D5 Receptors
Benzazepines
Dopamine D1 Receptors
Heterografts
Skeleton
Dopamine
Phosphotransferases
2,4-diaminopyrimidine

Keywords

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

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent c-Met/ALK multikinase inhibitory activities. / Liu, Zhiqing; Ai, Jing; Peng, Xia; Song, Zilan; Wu, Kui; Zhang, Jing; Yao, Qizheng; Chen, Yi; Ji, Yinchun; Yang, Yanhong; Geng, Meiyu; Zhang, Ao.

In: ACS Medicinal Chemistry Letters, Vol. 5, No. 4, 10.04.2014, p. 304-308.

Research output: Contribution to journalArticle

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, vol. 5, no. 4, pp. 304-308. https://doi.org/10.1021/ml400373j
Liu, Zhiqing ; Ai, Jing ; Peng, Xia ; Song, Zilan ; Wu, Kui ; Zhang, Jing ; Yao, Qizheng ; Chen, Yi ; Ji, Yinchun ; Yang, Yanhong ; Geng, Meiyu ; Zhang, Ao. / Novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent c-Met/ALK multikinase inhibitory activities. In: ACS Medicinal Chemistry Letters. 2014 ; Vol. 5, No. 4. pp. 304-308.
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AU - Yao, Qizheng

AU - Chen, Yi

AU - Ji, Yinchun

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