3-trifluoromethylbenzaldehyde-O-(2-carboxyphenoxy)oxime

• 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: 3-trifluoromethylbenzaldehyde-O-(2-carboxyphenoxy)oxime
• 英文别名: 2-[(E)-[3-(trifluoromethyl)phenyl]methylideneamino]oxybenzoic acid
• 化学式: C₁₅H₁₀F₃NO₃
• 分子量: 309.245
• InChiKey: JYEYMCMIADJBBB-DJKKODMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻氟苯甲酸 在 4-二甲氨基吡啶 、 lithium hydroxide 、 高氯酸 、 potassium tert-butylate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 3-trifluoromethylbenzaldehyde-O-(2-carboxyphenoxy)oxime
  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

• Bisaryloxime Ethers as Potent Inhibitors of Transthyretin Amyloid Fibril Formation
  作者：Steven M. Johnson、H. Michael Petrassi、Satheesh K. Palaninathan、Nilofar N. Mohamedmohaideen、Hans E. Purkey、Christopher Nichols、Kyle P. Chiang、Traci Walkup、James C. Sacchettini、K. Barry Sharpless、Jeffery W. Kelly

  DOI：10.1021/jm049274d

  日期：2005.3.1

  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.