3,4-Disubstituted isothiazoles: Novel potent inhibitors of VEGF receptors 1 and 2

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• 作者：Alex ; er S. Kiselyov ; Marina Semenova ; Victor V. Semenov
• 关键词：Angiogenesis ; ATP-competitive kinase inhibitors ; Vascular endothelial growth factor receptor 2 ; VEGFR-2 ; Isothiazoles
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 February 2009
• 年：2009
• 卷：19
• 期：4
• 页码：1195-1198
• 全文大小：277 K

文摘

Novel derivatives of isothiazoles are described as potent ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 inhibitory activity comparable to that of Vatalanib™ in both HTRF enzymatic and cellular assays. Several derivatives featuring bulky meta-substituents in the amide portion of the molecule displayed 4- to 8-fold specificity for VEGFR-2 versus VEGFR-1. Active molecules also showed high intrinsic permeability (>30 × 10⁻⁵ cm/min) across Caco-2 cell monolayer.