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

doi:10.1021/ml400373j

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	304-308
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	5
Issue number	4
DOIs	https://doi.org/10.1021/ml400373j
State	Published - Apr 10 2014
Externally published	Yes

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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10.1021/ml400373j

Cite this

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

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.",

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

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

year = "2014",

month = apr,

day = "10",

doi = "10.1021/ml400373j",

language = "English (US)",

volume = "5",

pages = "304--308",

journal = "ACS Medicinal Chemistry Letters",

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T1 - Novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent c-Met/ALK multikinase inhibitory activities

AU - Liu, Zhiqing

AU - Ai, Jing

AU - Peng, Xia

AU - Song, Zilan

AU - Wu, Kui

AU - Zhang, Jing

AU - Yao, Qizheng

AU - Chen, Yi

AU - Ji, Yinchun

AU - Yang, Yanhong

AU - Geng, Meiyu

AU - Zhang, Ao

PY - 2014/4/10

Y1 - 2014/4/10

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AB - 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.

KW - 2,4-diarylaminopyrimidine analogues

KW - C1-Substituted- N 3-benzazepine

KW - c-Met/ALK dual inhibitor

KW - structure repurposing

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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