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

Authors :: Sun, L.
Liang, C.
Shirazian, S.
Zhou, Y.
Miller, T.
Cui, J.
Fukuda, J. Y.
Chu, J.-Y.
Nematalla, A.
Wang, X.
Chen, H.
Sistla, A.
Luu, T. C.
Tang, F.
Wei, J.
Tang, C.
Source :: Journal of Medicinal Chemistry; March 2003, Vol. 46 Issue: 7 p1116-1119, 4p
Publication Year :: 2003
Abstract: 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 (<BO>12b</BO> or SU11248) has been found to show the best overall profile in terms of potency for the VEGF-R2 and PDGF-Rβ tyrosine kinase at biochemical and cellular levels, solubility, protein binding, and bioavailability. <BO>12b</BO> is currently in phase I clinical trials for the treatment of cancers.

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