27687-35-0Relevant articles and documents
Total spontaneous resolution by deracemization of isoindolinones
Yagishita, Fumitoshi,Ishikawa, Hiroki,Onuki, Tatsuo,Hachiya, Shoko,Mino, Takashi,Sakamoto, Masami
, p. 13023 - 13025 (2012)
Preferential crystallization is a powerful tool to obtain optically active materials from racemic mixtures without any chiral source, and has been utilized widely for optical resolution on large scales for example in industrial processes.[ 1] To resolve optically active materials by crystallization efficiently, dynamic preferential crystallization involving a racemization process, a so-called total spontaneous resolution, has been developed.[2] Many efforts have been invested in new variations of this method, and the racemization processes can be classified into three groups: 1) involving an intermediate enolate anion or enol at the a-position of a carbonyl group,[3] 2) involving atropisomerism of axially chiral materials,[4] and 3) involving an equilibrium reaction via an achiral intermediate.[5-7] We have now developed a new example of total spontaneous resolution of isoindolinones that involves a combination of an intramolecular equilibrium reaction via an achiral intermediate and preferential crystallization.
ISOINDOLIN-1-ONE DERIVATIVES
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Page/Page column 27-28; 37-38; 61, (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.
