Design, synthesis and pharmacological evaluation of 2-(thiazol-2- amino)-4-arylaminopyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors

Zhiqing Liu, Xihua Yue, Zilan Song, Xia Peng, Junfeng Guo, Yinchun Ji, Zhen Cheng, Jian Ding, Jing Ai, Meiyu Geng, Ao Zhang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) was developed by incorporation of a substituted 2-aminothiazole component as the C-2 substituent of the center pyrimidine core. Compound 5i showed highest potency of 12.4 nM against ALK and 24.1 nM against ALK gatekeeper mutation L1196M. Although only having moderate cellular potency in the SUP-M2 cells harboring NPM-ALK, compound 5i showed good kinase selectivity and dose-dependently inhibited phosphorylation of ALK and its down-stream signaling pathways.

Original languageEnglish (US)
Pages (from-to)438-448
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume86
Issue number1
DOIs
StatePublished - Oct 30 2014
Externally publishedYes

Fingerprint

Pharmacology
Phosphorylation
Phosphotransferases
Mutation
anaplastic lymphoma kinase
2-aminothiazole
pyrimidine

Keywords

  • 2,4-Diarylaminopyrimidine
  • 2-Aminothiazole
  • ALK kinase
  • Gatekeeper mutation
  • Non-small-cell lung cancer

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

Design, synthesis and pharmacological evaluation of 2-(thiazol-2- amino)-4-arylaminopyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors. / Liu, Zhiqing; Yue, Xihua; Song, Zilan; Peng, Xia; Guo, Junfeng; Ji, Yinchun; Cheng, Zhen; Ding, Jian; Ai, Jing; Geng, Meiyu; Zhang, Ao.

In: European Journal of Medicinal Chemistry, Vol. 86, No. 1, 30.10.2014, p. 438-448.

Research output: Contribution to journalArticle

Liu, Zhiqing ; Yue, Xihua ; Song, Zilan ; Peng, Xia ; Guo, Junfeng ; Ji, Yinchun ; Cheng, Zhen ; Ding, Jian ; Ai, Jing ; Geng, Meiyu ; Zhang, Ao. / Design, synthesis and pharmacological evaluation of 2-(thiazol-2- amino)-4-arylaminopyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 86, No. 1. pp. 438-448.
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AU - Song, Zilan

AU - Peng, Xia

AU - Guo, Junfeng

AU - Ji, Yinchun

AU - Cheng, Zhen

AU - Ding, Jian

AU - Ai, Jing

AU - Geng, Meiyu

AU - Zhang, Ao

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