2-Benzyl-3-chloro-3-phenylisoindolinone | 237769-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-Benzyl-3-chloro-3-phenylisoindolinone
• 英文别名: 2-benzyl-3-chloro-3-phenyl-2,3-dihydroisoindol-1-one；2-benzyl-3-chloro-3-phenyl-2,3-dihydroisoindolin-1-one；2-Benzyl-3-chloro-3-phenylisoindol-1-one
• CAS: 237769-24-3
• 化学式: C₂₁H₁₆ClNO
• 分子量: 333.817
• InChiKey: UFXIEIHEWOFOHA-UHFFFAOYSA-N

物化性质

• 沸点：
  498.8±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-Benzyl-3-chloro-3-phenylisoindolinone 在 N-碘代丁二酰亚胺 、 camphor-10-sulfonic acid 作用下， 以 四氢呋喃 为溶剂， 反应 76.0h， 生成 2-benzyl-3-phenethyloxy-3-phenyl-2,3-dihydro-1H-isoindol-1-one
  参考文献：
  名称：

  Small-Molecule Inhibitors of the MDM2-p53 Protein−Protein Interaction Based on an Isoindolinone Scaffold

  摘要：

  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 mu M) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (79; IC50) 5.3 (0.9 mu M), induced p53-dependent gene transcription, in a dose-dependent manner, in the MDM2 amplified, SJSA human sarcoma cell line.

  DOI：

  10.1021/jm0601194
• 作为产物：
  描述：

  邻苯甲酰苯甲酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 2-Benzyl-3-chloro-3-phenylisoindolinone
  参考文献：
  名称：

  Small-Molecule Inhibitors of the MDM2-p53 Protein−Protein Interaction Based on an Isoindolinone Scaffold

  摘要：

  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 mu M) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (79; IC50) 5.3 (0.9 mu M), induced p53-dependent gene transcription, in a dose-dependent manner, in the MDM2 amplified, SJSA human sarcoma cell line.

  DOI：

  10.1021/jm0601194

文献信息

• [EN] ISOINDOLIN-1-ONE DERIVATIVES<br/>[FR] DÉRIVÉS D'ISOINDOLIN-1-ONE
  申请人：CANCER REC TECH LTD

  公开号：WO2006024837A1

  公开（公告）日：2006-03-09

  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.

  式（1）的化合物或其前药和/或药用可接受的盐，其中X选择自O、N或S；R1选择自氢、卤素、羟基、取代或未取代的烷基、取代或未取代的羟基烷基、取代或未取代的烷基胺、烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基或杂环芳基；R2选择自氢、卤素、羟基、取代或未取代的烷基、取代或未取代的羟基烷基、取代或未取代的烷基胺、烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基或杂环芳基；R3选择自氢、卤素、羟基、取代或未取代的合金取代或未取代的羟基烷基、取代或未取代的烷基胺烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基或杂环芳基；R4-R7，用于表示独立选择自H、OH、烷基、烷氧基、烷基胺、羟基烷基、卤素、CF3、NH2、NO2、COOH、C=0的基团R4、R5、R6和R7。
• Synthesis of 3-Alkoxy- and 3-Alkylamino-2-alkyl-3-arylisoindolinones
  作者：Martin S. Kitching、William Clegg、Mark R. J. Elsegood、Roger J. Griffin、Bernard T. Golding

  DOI：10.1055/s-1999-3116

  日期：——

  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.

  溶剂控制的区域选择性使得3-氯异吲哚啉酮与初级胺的反应能够合理合成异吲哚啉酮，路线适合于平行组合化学。
• Isoindolin-1-One Derivatives
  申请人：Willems Hendrika Maria Gerarda

  公开号：US20080261917A1

  公开（公告）日：2008-10-23

  A compound of formula or a prodrug and/or a pharmaceutically acceptable salt thereof, wherein X is O, N or S; R 1 is 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; R 2 is 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; R 3 is 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 R 4 -R 7 , is used to represent groups R 4 , R 5 , R 6 and R 7 which are H, OH, alkyl, alkoxy, alkylamine, hydroxyalkyl, halo, CF 3 , NH 2 , NO 2 , COOH, C=0.

  该化合物的化学式为，或其前体药物和/或其药学上可接受的盐，其中X为O、N或S；R1为氢、卤、羟基、取代或未取代的烷基、取代或未取代的羟基烷基、取代或未取代的烷基胺、烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基烷基或杂环芳基烷基；R2为氢、卤、羟基、取代或未取代的烷基、取代或未取代的羟基烷基、取代或未取代的烷基胺、烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基烷基或杂环芳基烷基；R3为氢、卤、羟基、取代或未取代的烷基、取代或未取代的羟基烷基、取代或未取代的烷基胺、烷氧基、取代或未取代的芳基或杂环芳基、取代或未取代的芳基烷基或杂环芳基烷基；R4-R7用于代表R4、R5、R6和R7的基团，其为H、OH、烷基、烷氧基、烷基胺、羟基烷基、卤、CF3、NH2、NO2、COOH、C=0。
• Isoindolinone-based inhibitors of the MDM2–p53 protein–protein interaction
  作者：Ian R. Hardcastle、Shafiq U. Ahmed、Helen Atkins、A. Hilary Calvert、Nicola J. Curtin、Gillian Farnie、Bernard T. Golding、Roger J. Griffin、Sabrina Guyenne、Claire Hutton、Per Källblad、Stuart J. Kemp、Martin S. Kitching、David R. Newell、Stefano Norbedo、Julian S. Northen、Rebecca J. Reid、K. Saravanan、Henriëtte M.G. Willems、John Lunec

  DOI：10.1016/j.bmcl.2004.12.061

  日期：2005.3

  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.
• ISOINDOLIN-1-ONE DERIVATIVES
  申请人：Cancer Research Technology Limited

  公开号：EP1786773A1

  公开（公告）日：2007-05-23