5-溴-2,3-二氢-2-(苯基甲基)1H-异吲哚 | 905274-85-3

• 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
• 中文名称: 5-溴-2,3-二氢-2-(苯基甲基)1H-异吲哚
• 中文别名: 2-苄基-5-溴异吲哚
• 英文名称: 2-benzyl-5-bromoisoindoline
• 英文别名: 2-benzyl-5-bromo-2,3-dihydro-1H-isoindole；2-benzyl-5-bromo-1,3-dihydroisoindole
• CAS: 905274-85-3
• 化学式: C₁₅H₁₄BrN
• 分子量: 288.187
• InChiKey: RUTQXTMEZOZGLF-UHFFFAOYSA-N

物化性质

• 沸点：
  345.5±42.0 °C(Predicted)
• 密度：
  1.412±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-溴-2,3-二氢-2-(苯基甲基)1H-异吲哚 在 正丁基锂 、 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~30.0 ℃ 、101.33 kPa 条件下， 反应 92.5h， 生成 N-methylisoindoline-5-carboxamide
  参考文献：
  名称：

  Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit

  摘要：

  A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an a-amino amide zincbinding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol(-1) in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol(-1) greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol(-1), ascribed to additional binding interactions within the N-epsilon-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions.

  DOI：

  10.1016/j.bmcl.2019.126926
• 作为产物：
  描述：

  2-苄基-5-溴-1H-异吲哚-1,3(2H)-二酮 在 sodium tetrahydroborate 、 三氟化硼乙醚 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以82%的产率得到5-溴-2,3-二氢-2-(苯基甲基)1H-异吲哚
  参考文献：
  名称：

  Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit

  摘要：

  A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an a-amino amide zincbinding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol(-1) in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol(-1) greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol(-1), ascribed to additional binding interactions within the N-epsilon-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions.

  DOI：

  10.1016/j.bmcl.2019.126926

文献信息

• Heterocyclic-substituted phenyl methanones
  申请人：Jolidon Synese

  公开号：US20060178381A1

  公开（公告）日：2006-08-10

  The present invention relates to compounds of formula I wherein R 1 , R 2 , and are defined in the specification and to pharmaceutically acceptable acid addition salts thereof.

  本发明涉及式I的化合物 其中 R 1 ， R 2 ，并在规范中定义，并且其药学上可接受的酸盐。
• HETEROCYCLIC-SUBSTITUTED PHENYL METHANONES
  申请人：Jolidon Synese

  公开号：US20090203665A1

  公开（公告）日：2009-08-13

  The present invention relates to compounds of formula I wherein R 1 , R 2 , and are defined in the specification and to pharmaceutically acceptable acid addition salts thereof.

  本发明涉及式I的化合物，其中R1，R2和在规范中定义，并且其药学上可接受的酸加合盐。
• Practical synthesis of isoindolines yields potent colistin potentiators for multidrug-resistant Acinetobacter baumannii
  作者：Somnath Dutta、Samantha Eyolfson、Yuhang Zhu、Yuefeng Gao、Xiang Wang

  DOI：10.1039/d4ob00463a

  日期：——

  An efficient and practical one-pot synthesis of isoindolines from readily available starting materials was achieved under mild conditions by implementing an isoindole umpolung strategy. A variety of isoindolines were prepared with good to excellent yields. Biological screens of these identified compounds demonstrated that they are potent potentiators of colistin for multi-drug resistant Acinetobacter

  通过实施异吲哚翻转策略，在温和条件下，从容易获得的起始原料中高效实用地一锅法合成异吲哚啉。制备了多种异吲哚啉，产率良好至优异。这些已鉴定化合物的生物学筛选表明，它们是粘菌素对多重耐药鲍曼不动杆菌的有效增强剂。
• Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors
  作者：Emmanuel Pinard、Daniela Alberati、Markus Bender、Edilio Borroni、Virginie Brom、Serge Burner、Holger Fischer、Dominik Hainzl、Remy Halm、Nicole Hauser、Synèse Jolidon、Judith Lengyel、Hans-Peter Marty、Thierry Meyer、Jean-Luc Moreau、Roland Mory、Robert Narquizian、Roger D. Norcross、Philipp Schmid、Roger Wermuth、Daniel Zimmerli

  DOI：10.1016/j.bmcl.2010.09.124

  日期：2010.12

  Benzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. SAR studies and subsequent lead optimization efforts focused primarily on addressing hERG liability and on improving in vivo efficacy resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo PD and PK profiles. (C) 2010 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC SUBSTITUTED PHENYL METHANONES AS INHIBITORS OF THE GLYCINE TRANSPORTER 1
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1848694B1

  公开（公告）日：2009-11-25