N-(3,5-二氯苯氧基)邻苯二甲酰亚胺 | 849048-57-3

• 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: N-(3,5-二氯苯氧基)邻苯二甲酰亚胺
• 英文名称: N-(3,5-dichlorophenoxy)phthalimide
• 英文别名: 2-(3,5-Dichlorophenoxy)isoindole-1,3-dione
• CAS: 849048-57-3
• 化学式: C₁₄H₇Cl₂NO₃
• 分子量: 308.12
• InChiKey: PMWWRRXOCPYAJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3,5-二氯苯氧基)邻苯二甲酰亚胺 在 一水合肼 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 12.0h， 以92%的产率得到O-(3,5-二氯苯基)羟胺
  参考文献：
  名称：

  Bisaryloxime Ethers as Potent Inhibitors of Transthyretin Amyloid Fibril Formation

  摘要：

  Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring rate-limiting tetramer dissociation and monomer misfolding, is implicated in several human diseases. Amyloidogenesis can be inhibited through native state stabilization, mediated by small molecule binding to TTR's primarily unoccupied thyroid hormone binding sites. New native state stabilizers have been discovered herein by the facile condensation of arylaldehydes with aryloxyamines affording a bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively stabilize the native tetrameric state of TTR over the dissociative transition state under amyloidogenic conditions, leading to an increase in the dissociation activation barrier. Several bisaryloxime ethers bind selectively to TTR in human blood plasma over the plethora of other plasma proteins, a necessary attribute for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation by N-O bond cleavage, this process is slowed by their binding to TTR. Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow relative to the half-life of plasma TTR. The bisaryloxime ether library provides valuable structure-activity relationship insight for the development of structurally analogous inhibitors with superior stability profiles, should that prove necessary.

  DOI：

  10.1021/jm049274d
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 3,5-二氯苯硼酸 在 吡啶 、 4 A molecular sieve 、 copper(l) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 48.0h， 以45%的产率得到N-(3,5-二氯苯氧基)邻苯二甲酰亚胺
  参考文献：
  名称：

  Bisaryloxime Ethers as Potent Inhibitors of Transthyretin Amyloid Fibril Formation

  摘要：

  Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring rate-limiting tetramer dissociation and monomer misfolding, is implicated in several human diseases. Amyloidogenesis can be inhibited through native state stabilization, mediated by small molecule binding to TTR's primarily unoccupied thyroid hormone binding sites. New native state stabilizers have been discovered herein by the facile condensation of arylaldehydes with aryloxyamines affording a bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively stabilize the native tetrameric state of TTR over the dissociative transition state under amyloidogenic conditions, leading to an increase in the dissociation activation barrier. Several bisaryloxime ethers bind selectively to TTR in human blood plasma over the plethora of other plasma proteins, a necessary attribute for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation by N-O bond cleavage, this process is slowed by their binding to TTR. Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow relative to the half-life of plasma TTR. The bisaryloxime ether library provides valuable structure-activity relationship insight for the development of structurally analogous inhibitors with superior stability profiles, should that prove necessary.

  DOI：

  10.1021/jm049274d

文献信息

• Inhibitors of transthyretin amyloid fibril formation
  申请人：Kelly W. Jeffery

  公开号：US20060178527A1

  公开（公告）日：2006-08-10

  Bisaryloxime ethers and bisarylhydroazones are shown to be effective for inhibiting formation of amyloid fibrils of transthyretin.

  Bisaryloxime醚和bisarylhydroazones被证明对抑制甲状腺前蛋白淀粉样纤维的形成有效。
• Inhibitors of Transthyretin Amyloid Fibril Formation
  申请人：Kelly Jeffery W.

  公开号：US20090054629A1

  公开（公告）日：2009-02-26

  Bisaryloxime ethers and bisarylhydroazones are shown to be effective for inhibiting formation of amyloid fibrils of transthyretin.

  Bisaryloxime醚和bisarylhydroazones已被证明对抑制转甲状腺原蛋白淀粉样纤维的形成具有有效性。
• INHIBITORS OF TRANSTHYRETIN AMYLOID FIBRIL FORMATION
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：EP1848688A2

  公开（公告）日：2007-10-31
• US7312361B2
  申请人：——

  公开号：US7312361B2

  公开（公告）日：2007-12-25
• [EN] INHIBITORS OF TRANSTHYRETIN AMYLOID FIBRIL FORMATION<br/>[FR] INHIBITEURS DE LA FORMATION DE FIBRILLES AMYLOIDES DE TRANSTHYRETINE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2006086517A2

  公开（公告）日：2006-08-17

  [EN] Bisaryloxime ethers and bisarylhydroazones are shown to be effective for inhibiting formation of amyloid fibrils of transthyretin.
  [FR] Selon l'invention, les éthers de bisaryloxime et les bisarylhydroazones sont efficaces dans l'inhibition de la formation de fibrilles amyloïdes de transthyrétine.