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
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
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DOI：
10.1021/jm0204183
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发表时间：
2003-03-27
影响因子：
7.3
通讯作者：
Tang, C
中科院分区：
文献类型：
--
作者：
Sun, L;Liang, C;Tang, C
为了提高吲哚啉-2-酮的抗肿瘤活性，优化其溶解性和蛋白结合等药理学性质，设计并合成了一系列不同碱性和弱碱性的吲哚啉-2-酮类似物。已发现5-[5-氟-2-氧代-1，2-二氢吲哚-（3 Z）-亚甲基]-2，4-二甲基-1H-吡咯-3-羧酸（2-二乙基氨基乙基）酰胺（12 b或SU 11248）在生物化学和细胞水平上对VEGF-R2和PDGF-R β酪氨酸激酶的效力、溶解度、蛋白结合和生物利用度方面显示出最佳的总体特征。12 b目前正在进行治疗癌症的I期临床试验。
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.