878022-32-3Relevant academic research and scientific papers
New Therapeutic Agents
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Page/Page column 35, (2011/10/04)
A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold
Hardcastle, Ian R.,Ahmed, Shafiq U.,Atkins, Helen,Farnie, Gillian,Golding, Bernard T.,Griffin, Roger J.,Guyenne, Sabrina,Hutton, Claire,K?llblad, Per,Kemp, Stuart J.,Kitching, Martin S.,Newell, David R.,Norbedo, Stefano,Northen, Julian S.,Reid, Rebecca J.,Saravanan,Willems, Henri?tte M. G.,Lunec, John
, p. 6209 - 6221 (2007/10/03)
From a set of weakly potent lead compounds, using in silico screening and small library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been identified as inhibitors of the MDM2-p53 interaction. Two of the most potent compounds, 2-benzyl-3-(4-chlorophenyl)-3-(3-hydroxypropoxy)-2,3- dihydroisoindol-1-one (76; IC50 = 15.9 ± 0.8 μM) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2, 3-dihydroisoindol-1-one (79; IC50 = 5.3 ± 0.9 μM), induced p53-dependent gene transcription, in a dose-dependent manner, in the MDM2 amplified, SJSA human sarcoma cell line.
ISOINDOLIN-1-ONE DERIVATIVES
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Page/Page column 56-57, (2010/10/20)
A compound of formula (1) or a prodrug and/or pharmaceutically acceptable salt thereof, wherein X is selected from O, N or S; R1 is selected from hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroaralkyl; R2 is selected from hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl substituted or unsubstituted alkylamine, alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; R3 is selected from hydrogen, halo, hydroxy, substituted or unsubstituted alloy substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine alkoxy, substituted or unsubstituted aryl or heteroaryl, and substituted or unsubstituted aralkyl or heteroalkyl; and R4-R7, is used to represent groups R4, R5, R6 and R7 which are independently selected from H, OH, alkyl, alkoxy, alkylamine, hydroxyalkyl, halo, CF3, NH2, NO2, COOH, C=0.
Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction
Hardcastle, Ian R.,Ahmed, Shafiq U.,Atkins, Helen,Calvert, A. Hilary,Curtin, Nicola J.,Farnie, Gillian,Golding, Bernard T.,Griffin, Roger J.,Guyenne, Sabrina,Hutton, Claire,Kaellblad, Per,Kemp, Stuart J.,Kitching, Martin S.,Newell, David R.,Norbedo, Stefano,Northen, Julian S.,Reid, Rebecca J.,Saravanan,Willems, Henriette M.G.,Lunec, John
, p. 1515 - 1520 (2007/10/03)
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 μM in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line.
