2-(biphenyl-2-ylmethyl)-N-(tert-butyl)-5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamide | 1002557-14-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(biphenyl-2-ylmethyl)-N-(tert-butyl)-5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamide
• 英文别名: N-tert-butyl-5-hydroxy-4-methyl-3-oxo-2-[(2-phenylphenyl)methyl]-1H-isoindole-1-carboxamide
• CAS: 1002557-14-3
• 化学式: C₂₇H₂₈N₂O₃
• 分子量: 428.531
• InChiKey: FZIZRJKMCCBMMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(biphenyl-2-ylmethyl)-N-(tert-butyl)-5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamide 、 溴氟甲烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以63%的产率得到2-(biphenyl-2-ylmethyl)-N-(tert-butyl)-5-(fluoromethoxy)-4-methyl-3-oxoisoindoline-1-carboxamide
  参考文献：
  名称：

  Isoindolinone compounds active as Kv1.5 blockers identified using a multicomponent reaction approach

  摘要：

  A series of isoindolinone compounds have been developed showing good in vitro potency on the Kv1.5 ion channel. By modification of two side chains on the isoindolinone scaffold, metabolically stable compounds with good in vivo PK profile could be obtained leaving the core structure unsubstituted. In this way, low microsomal intrinsic clearance (CLint) could be achieved despite a relatively high logD. The compounds were synthesized using the Ugi reaction, in some cases followed by Suzuki and Diels-Alder reactions, giving a diverse set of compounds in a small number of reaction steps. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.081
• 作为产物：
  描述：

  2-苯基苄胺 在 ytterbium(III) triflate 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 1.5h， 生成 2-(biphenyl-2-ylmethyl)-N-(tert-butyl)-5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamide
  参考文献：
  名称：

  Isoindolinone compounds active as Kv1.5 blockers identified using a multicomponent reaction approach

  摘要：

  A series of isoindolinone compounds have been developed showing good in vitro potency on the Kv1.5 ion channel. By modification of two side chains on the isoindolinone scaffold, metabolically stable compounds with good in vivo PK profile could be obtained leaving the core structure unsubstituted. In this way, low microsomal intrinsic clearance (CLint) could be achieved despite a relatively high logD. The compounds were synthesized using the Ugi reaction, in some cases followed by Suzuki and Diels-Alder reactions, giving a diverse set of compounds in a small number of reaction steps. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.081

文献信息

• NEW COMPOUNDS I/418
  申请人：Bjore Annika

  公开号：US20080015237A1

  公开（公告）日：2008-01-17

  There is provided compounds of formula I, wherein R 1 to R 7 have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.

  提供了式I的化合物， 其中R1至R7在描述中给出了它们的含义，这些化合物在预防和治疗心律失常方面非常有用，特别是房性和室性心律失常。
• ISOINDOLINE DERIVATIVES FOR THE TREATMENT OF ARRHYTHMIAS
  申请人：AstraZeneca AB

  公开号：EP2049484A1

  公开（公告）日：2009-04-22
• Isoindoline Derivatives For The Treatment Of Arrhythmias
  申请人：Bjore Annika

  公开号：US20100298392A1

  公开（公告）日：2010-11-25

  There is provided compounds of formula I, wherein R 1 to R 7 have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
• [EN] ISOINDOLINE DERIVATIVES FOR THE TREATMENT OF ARRHYTHMIAS<br/>[FR] DÉRIVÉS D'ISOINDOLINE DANS LE TRAITEMENT DES ARYTHMIES
  申请人：ASTRAZENECA AB

  公开号：WO2008008022A1

  公开（公告）日：2008-01-17

  [EN] There is provided compounds of formula I, wherein R¹ to R⁷ have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
  [FR] La présente invention concerne des composés de formule I, où R¹ à R⁷ ont les valeurs données dans la description, qui peuvent être employés dans le traitement prophylactique et thérapeutique des arythmies, en particulier des arythmies auriculaires et ventriculaires.