Design, synthesis, and biological evaluation of novel 3-aryl-4-(1 H-indole-3yl)-1, 5-dihydro-2 H-pyrrole-2-ones as vascular endothelial growth factor receptor (VEGF-R …

C Peifer, R Selig, K Kinkel, D Ott, F Totzke…

Index: Peifer, Christian; Stoiber, Thomas; Unger, Eberhard; Totzke, Frank; Schaechtele, Christoph; Marme, Dieter; Brenk, Ruth; Klebe, Gerhard; Schollmeyer, Dieter; Dannhardt, Gerd Journal of Medicinal Chemistry, 2006 , vol. 49, # 4 p. 1271 - 1281

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Citation Number: 43

Abstract

In this study we report on the design, synthesis, and biological evaluation of pyrrole-2-one 2 to be a highly potent VEGF-R2/3 inhibitor with IC50 of 31/37 nM. The novel 3, 4-diaryl-2 H- pyrrole-2-ones were designed on the basis of the modeled binding mode of the corresponding 1 H-pyrrole-2, 5-dione (maleimide) VEGF-R2/3 inhibitor 1 indicating two H- bond ligand− protein interactions in the ATP pocket for the amide 2 but not for the isomer 3 ...