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.

中文翻译：

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新型酪氨酸5- [5-氟-2-氧代-1,2-二氢吲哚-（3Z）-亚甲基] -2,4-二甲基-1H-吡咯-3-羧酸（2-二乙基氨基乙基）酰胺的发现靶向血管内皮和血小板衍生的生长因子受体酪氨酸激酶的激酶抑制剂。

为了改善抗肿瘤特性并优化包括吲哚-2-酮的溶解度和蛋白质结合在内的药物特性，设计并合成了许多不同的碱性和弱碱性类似物。5- [5-氟-2-氧代-1,2，二氢吲哚-（3Z）-亚甲基] -2,4-二甲基-1H-吡咯-3-羧酸（2-二乙基氨基乙基）酰胺（12b或SU11248）具有已发现在生化和细胞水平，溶解度，蛋白质结合和生物利用度方面，VEGF-R2和PDGF-Rbeta酪氨酸激酶的效能表现出最佳的总体特征。12b目前处于治疗癌症的I期临床试验中。