Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction

摘要

A series of 2-N-alkyl-3-aryl-3-alkoxyisoindolinones has been synthesised and evaluated as inhibitors of the MDM2-p53 interaction. The most potent compound, 3-(4-chlorophenyl)-3-(4- hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1- one (NU8231), exhibited an IC50 of 5.3 +/- 0.9 mu M in an ELISA assay, and induced p53-dependent gene transcription in a dose- dependent manner, in the SJSA human sarcoma cell line. (c) 2005 Elsevier Ltd. All rights reserved.