Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors

Efforts to correct hERG inhibition

Yuanxiang Wang, Jing Ai, Jinfeng Yue, Xia Peng, Yinchun Ji, Ailing Zhao, Xin Gao, Ying Wang, Yi Chen, Gang Liu, Zhaobing Gao, Meiyu Geng, Ao Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A preclinical study on our previously discovered highly potent c-Met inhibitor 1 (zgwatinib) demonstrated its significant toxicity, and a SAR campaign was conducted to finely tune down the hERG inhibition without affecting the c-Met potency. Compounds 11, 12 and 39 stood out as new c-Met inhibitors with IC50 values of <3.0 nM and being nearly inactive against hERG channels.

Original languageEnglish (US)
Pages (from-to)1423-1427
Number of pages5
JournalMedChemComm
Volume3
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Fingerprint

Protein-Tyrosine Kinases
Inhibitory Concentration 50
Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors : Efforts to correct hERG inhibition. / Wang, Yuanxiang; Ai, Jing; Yue, Jinfeng; Peng, Xia; Ji, Yinchun; Zhao, Ailing; Gao, Xin; Wang, Ying; Chen, Yi; Liu, Gang; Gao, Zhaobing; Geng, Meiyu; Zhang, Ao.

In: MedChemComm, Vol. 3, No. 11, 01.11.2012, p. 1423-1427.

Research output: Contribution to journalArticle

Wang, Y, Ai, J, Yue, J, Peng, X, Ji, Y, Zhao, A, Gao, X, Wang, Y, Chen, Y, Liu, G, Gao, Z, Geng, M & Zhang, A 2012, 'Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors: Efforts to correct hERG inhibition', MedChemComm, vol. 3, no. 11, pp. 1423-1427. https://doi.org/10.1039/c2md20192e
Wang, Yuanxiang ; Ai, Jing ; Yue, Jinfeng ; Peng, Xia ; Ji, Yinchun ; Zhao, Ailing ; Gao, Xin ; Wang, Ying ; Chen, Yi ; Liu, Gang ; Gao, Zhaobing ; Geng, Meiyu ; Zhang, Ao. / Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors : Efforts to correct hERG inhibition. In: MedChemComm. 2012 ; Vol. 3, No. 11. pp. 1423-1427.
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AU - Gao, Xin

AU - Wang, Ying

AU - Chen, Yi

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