(4-[(E)-2-(3,5-dihydroxyphenyl)vinyl]phenyl)-boronic acid | 1266682-74-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (4-[(E)-2-(3,5-dihydroxyphenyl)vinyl]phenyl)-boronic acid
• 英文别名: {4-[(E)-2-(3,5-Dihydroxyphenyl)ethenyl]phenyl}boronic Acid；[4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]phenyl]boronic acid
• CAS: 1266682-74-9
• 化学式: C₁₄H₁₃BO₄
• 分子量: 256.066
• InChiKey: DYVLARRBNBVUFX-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.95
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,5-二甲氧基溴苄 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium periodate 、 potassium acetate 、 三溴化硼 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 8.33h， 生成 (4-[(E)-2-(3,5-dihydroxyphenyl)vinyl]phenyl)-boronic acid
  参考文献：
  名称：

  Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation

  摘要：

  Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR. ligand complexes. The ensuing structure-function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. These findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.

  DOI：

  10.1021/acs.jmedchem.7b00952

文献信息

• Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation
  作者：Thomas P. Smith、Ian W. Windsor、Katrina T. Forest、Ronald T. Raines

  DOI：10.1021/acs.jmedchem.7b00952

  日期：2017.9.28

  Transthyretin (TTR) is a homotetrameric protein. Its dissociation into monomers leads to the formation of fibrils that underlie human amyloidogenic diseases. The binding of small molecules to the thyroxin-binding sites in TTR stabilizes the homotetramer and attenuates TTR amyloidosis. Herein, we report on boronic acid-substituted stilbenes that limit TTR amyloidosis in vitro. Assays of affinity for TTR and inhibition of its tendency to form fibrils were coupled with X-ray crystallographic analysis of nine TTR. ligand complexes. The ensuing structure-function data led to a symmetrical diboronic acid that forms a boronic ester reversibly with serine 117. This diboronic acid inhibits fibril formation by both wild-type TTR and a common disease related variant, V30M TTR, as effectively as does tafamidis, a small-molecule drug used to treat TTR-related amyloidosis in the clinic. These findings establish a new modality for covalent inhibition of fibril formation and illuminate a path for future optimization.