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

doi:10.1039/c2md20192e

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 journal › Article › peer-review

8 Scopus citations

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 language	English (US)
Pages (from-to)	1423-1427
Number of pages	5
Journal	MedChemComm
Volume	3
Issue number	11
DOIs	https://doi.org/10.1039/c2md20192e
State	Published - Nov 2012
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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10.1039/c2md20192e

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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.",

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

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T1 - Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors

T2 - Efforts to correct hERG inhibition

AU - Wang, Yuanxiang

AU - Ai, Jing

AU - Yue, Jinfeng

AU - Peng, Xia

AU - Ji, Yinchun

AU - Zhao, Ailing

AU - Gao, Xin

AU - Wang, Ying

AU - Chen, Yi

AU - Liu, Gang

AU - Gao, Zhaobing

AU - Geng, Meiyu

AU - Zhang, Ao

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

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Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors: Efforts to correct hERG inhibition

Abstract

ASJC Scopus subject areas

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