68972-64-5Relevant academic research and scientific papers
Eosin Y as a Redox Catalyst and Photosensitizer for Sequential Benzylic C?H Amination and Oxidation
Yan, Dong-Mei,Zhao, Quan-Qing,Rao, Li,Chen, Jia-Rong,Xiao, Wen-Jing
, p. 16895 - 16901 (2018/10/26)
A new synergistic multicatalytic activation mode of eosin Y has been discovered by exploiting the redox potential of its ground state and excited state. This catalytic strategy proves to be an enabling tool for visible-light-driven sequential benzylic C?H amination and oxidation of o-benzyl-N-methoxyl-benzamides when using Selectfluor as a hydrogen atom transfer (HAT) reagent and O2 as oxidant. Efficient synthesis of a range of diversely functionalized 3-hydroxyisoindolinones can thus be achieved with good yields and selectivity at mild reaction conditions. Preliminary mechanistic studies and DFT calculations suggest that eosin Y works as a redox catalyst and photosensitizer.
3-hydroxy isoindole-1-ketone derivative and preparation method thereof
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Paragraph 0075; 0076; 0077; 0078, (2017/11/04)
The invention discloses a preparation method of a 3-hydroxy isoindole-1-ketone derivative (formula 2). A compound as shown by formula (1) is used for carrying out substitution reaction in a solvent in the presence of alkali and air to obtain the 3-hydroxy
Base-promoted cascade C-C coupling/N-α-sp3C-H hydroxylation for the regiospecific synthesis of 3-hydroxyisoindolinones
Shen, Jinhai,You, Qihua,Fu, Qi,Kuai, Changsheng,Huang, Huabin,Zhao, Li,Zhuang, Zhixia
, p. 5170 - 5173 (2017/11/06)
A base-promoted cascade reaction for the regiospecific synthesis of substituted 3-hydroxyisoindolinones under transition-metal-free conditions is developed. The base-mediated C-C bond coupling and N-α-sp3C-H bond hydroxylation are involved in t
A direct arylation-oxidation route to 3-arylisoindolinone inhibitors of MDM2-p53 interaction
Dempster, Richard K.,Luzzio, Frederick A.
, p. 4992 - 4995 (2011/10/08)
A route to the MDM2-p53 inhibitor isoindolinone pharmacophore from a pre-formed phthalimide is detailed. The route involves treatment of 3-hydroxy-2-(n-propyl)isoindolinone with a substituted benzene in the presence of triflic acid. The resulting 3-aryl-2-(n-propyl)isoindolinones are then oxidized to the corresponding 3-hydroxy-3-aryl-2-(n-propyl) isoindolinones by treatment with 2,2'-bipyridinium chlorochromate. The benzylic oxidation represents a rather rare oxochromium (VI)-mediated reaction in which a selective C-H to C-OH transformation occurs.
Isoindolinone inhibitors of the murine double minute 2 (MFM2)-p53 protein-protein interaction: Structure-activity studies leading to improved potency
Hardcastle, Ian R.,Liu, Junfeng,Valeur, Eric,Watson, Anna,Ahmed, Shafiq U.,Blackburn, Timothy J.,Bennaceur, Karim,Clegg, William,Drummond, Catherine,Endicott, Jane A.,Golding, Bernard T.,Griffin, Roger J.,Gruber, Jan,Haggerty, Karen,Harrington, Ross W.,Hutton, Claire,Kemp, Stuart,Lu, Xiaohong,McDonnell, James M.,Newell, David R.,Noble, Martin E. M.,Payne, Sara L.,Revill, Charlotte H.,Riedinger, Christiane,Xu, Qing,Lunec, John
, p. 1233 - 1243 (2011/05/07)
Inhibition of the MDM2-p53 interaction has been shown to produce an antitumor effect, especially in MDM2 amplified tumors. The isoindolinone scaffold has proved to be versatile for the discovery of MDM2-p53 antagonists. Optimization of previously reported inhibitors, for example, NU8231 (7) and NU8165 (49), was guided by MDM2 NMR titrations, which indicated key areas of the binding interaction to be explored. Variation of the 2-N-benzyl and 3-alkoxy substituents resulted in the identification of 3-(4-chlorophenyl)-3-((1- (hydroxymethyl)cyclopropyl)methoxy)-2-(4-nitrobenzyl)isoindolin-1-one (74) as a potent MDM2-p53 inhibitor (IC50 = 0.23 A± 0.01 μM). Resolution of the enantiomers of 74 showed that potent MDM2-p53 activity primarily resided with the (+)-R-enantiomer (74a; IC50 = 0.17 A± 0.02 μM). The cellular activity of key compounds has been examined in cell lines with defined p53 and MDM2 status. Compound 74a activates p53, MDM2, and p21 transcription in MDM2 amplified cells and shows moderate selectivity for wild-type p53 cell lines in growth inhibition assays.
New Therapeutic Agents
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, (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.
ISOINDOLIN-1-ONE DERIVATIVES
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Page/Page column 56, (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.
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.
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.
