Discovery of 5-[5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase

被引：433

作者：

Sun, L ^{[1
]}

Liang, C ^{[1
]}

Shirazian, S ^{[1
]}

Zhou, Y ^{[1
]}

Miller, T ^{[1
]}

Cui, J ^{[1
]}

Fukuda, JY ^{[1
]}

Chu, JY ^{[1
]}

Nematalla, A ^{[1
]}

Wang, XY ^{[1
]}

Chen, H ^{[1
]}

Sistla, A ^{[1
]}

Luu, TC ^{[1
]}

Tang, F ^{[1
]}

Wei, J ^{[1
]}

Tang, C ^{[1
]}

机构：

[1] Sugen Inc, San Francisco, CA 94080 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 07期

关键词：

D O I：

10.1021/jm0204183

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To improve the antitumor properties and optimize the pharmaceutical properties including solubility and protein binding of indolin-2-ones, a number of different basic and weakly basic analogues were designed and synthesized. 5-[5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl- 1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide (12b or SU11248) has been found to show the best overall profile in terms of potency for the VEGF-R2 and PDGF-Rbeta tyrosine kinase at biochemical and cellular levels, solubility, protein binding, and bioavailability. 12b is currently in phase I clinical trials for the treatment of cancers.

引用

页码：1116 / 1119

页数：4

共 12 条

[1] New paradigms for the treatment of cancer: The role of anti-angiogenesis agents [J].