27687-35-0Relevant academic research and scientific papers
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.
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.
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.
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.
Synthesis of 3-alkoxy- and 3-alkylamino-2-alkyl-3-arylisoindolinones
Kitching, Martin S.,Clegg, William,Elsegood, Mark R. J.,Griffin, Roger J.,Golding, Bernard T.
, p. 997 - 999 (2007/10/03)
Solvent-controlled regioselectivity in the reactions of 3- chloroisoindolinones with primary amines allows the rational synthesis of isoindolinones by a route suitable for parallel combinatorial chemistry.
Pseudoacids. II. 2-Acylbenzoic Acid Derivatives
Valente, Edward J.,Martin, Samuel B.,Sullivan, Larry D.
, p. 264 - 276 (2007/10/03)
Structures of derivatives of cyclic o-acylbenzoic acids, including the chloride, endo- and exocyclic amides, esters and anhydrides, are examined. 3-Chloro-1(3H)-isobenzofuranone (1), orthorhombic, Pbca, a = 11.616 (5), b = 8.120 (3), c = 15.640 (9) A; 3-methoxy-3-phenyl-1(3H)-isobenzofuranone (3), orthorhombic, P212121, a = 6.923 (2), b = 8.291 (4), c = 21.551 (8) A; 3-hydroxy-3-phenyl-N-propyl-1(3H)-isoindolone (4), orthorhombic, P212121, a = 8.662 (4), b = 9.551 (7), c = 17.649 (14) A; 3-(N-morpholino)-1(3H)-isobenzofuranone (5), triclinic, P1, a = 6.172 (4), b = 11.163 (7), c = 17.33 (2) A, α = 105.91 (6), β = 99.85 (6), γ = 97.57 (5)°; 3-(2′-benzoylbenzoyloxy)-3-phenyl-1(3H)-isobenzofuranone (7), triclinic, P1, a = 9.694 (3), b = 10.505 (4), c = 11.163 (4) A°, α = 80.58 (3), β = 80.41 (3), γ = 76.49 (3)°; bis[1(3H)-isobenzofuranone-3-yl]ether (8), monoclinic, I2/a, a = 15.31 (2), b = 6.111 (12), c = 28.30 (5) A, β = 101.61 (12)°. An open oxoacid tertiary amide is also described: N-morpholino 2′-benzoylbenzamide (6): monoclinic, P21/c, a = 6.844 (4), b = 15.696 (8), c = 14.154 (7) A, β = 99.43 (4)°. Pseudoacid derivatives form planar isobenzofuran and isoindole rings, and the former aldehyde/ketone carbon-heteroatom endocyclic and exocyclic bond distances show bond length variations which correlate with the relative basicities of the attached groups. Structures of both endocyclic and exocyclic nitrogen pseudoamides are reported as well as examples of the normal-pseudoanhydride and the dipseudoanhydride.
Preparation of 3-Hydroxyindolin-1-ones and o-Acylbenzamides. A Study of Ring-Chain Tautomerism
Nishio, Takehiko,Yamamoto, Hiroshi
, p. 883 - 892 (2007/10/02)
3-Hydroxyisoindolinones (ring form) as well as their chain tautomers, o-acylbenzamides, were prepared from the reactions of 3-benzalphthalide 1, 3-halophthalides 3, and o-acylbenzoic acids 6 or their esters 7 with amines 2, and those of phthalimides 4 wit
