Literature

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 (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.

DOI： 10.1021/jm0204183

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

Journal of Medicinal Chemistry 2003.0

Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

Bioorganic & Medicinal Chemistry Letters 2013.0

N4-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d]pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation

Bioorganic & Medicinal Chemistry 2012.0

Identification of Substituted 3-[(4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene]- 1,3-dihydroindol-2-ones as Growth Factor Receptor Inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rβ Tyrosine Kinases

Journal of Medicinal Chemistry 2000.0

Synthesis and evaluation of novel 5-sulfonyl-indolin-2-ones as potent cytotoxic agents

MedChemComm 2011.0

The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors