(E)-(4-((4-((1-(4-fluorobenzyl)-3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid | 1312201-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (E)-(4-((4-((1-(4-fluorobenzyl)-3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid
• 英文别名: [4-[[4-[(E)-[1-[(4-fluorophenyl)methyl]-3-methyl-2,5-dioxoimidazolidin-4-ylidene]methyl]phenoxy]methyl]phenyl]boronic acid
• CAS: 1312201-64-1
• 化学式: C₂₅H₂₂BFN₂O₅
• 分子量: 460.269
• InChiKey: HKSLBTZOOODZEW-OEAKJJBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  90.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[(4-溴苄基)氧基]苯甲醛 在 哌啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium periodate 、 potassium acetate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 44.5h， 生成 (E)-(4-((4-((1-(4-fluorobenzyl)-3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid 、 (Z)-(4-((4-((1-(4-fluorobenzyl)-3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid
  参考文献：
  名称：

  Structure-Based Design of Novel Boronic Acid-Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described a boronic add-based inhibitor of ATX, named HA155 (1). Here, we report the design of new inhibitors based on the crystal structure of ATX in complex with inhibitor 1. Furthermore, we describe the syntheses and activities of these new inhibitors, whose potencies can be explained by structural data. To understand the difference in activity between two different isomers with nanomolar potencies, we performed molecular docking experiments. Intriguingly, molecular docking suggested a remarkable binding pose for one of the isomers, which differs from the original binding pose of inhibitor 1 for ATX, opening further options for inhibitor design.

  DOI：

  10.1021/jm200310q

文献信息

• Structure-Based Design of Novel Boronic Acid-Based Inhibitors of Autotaxin
  作者：Harald M. H. G. Albers、Loes J. D. Hendrickx、Rob J. P. van Tol、Jens Hausmann、Anastassis Perrakis、Huib Ovaa

  DOI：10.1021/jm200310q

  日期：2011.7.14

  Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described a boronic add-based inhibitor of ATX, named HA155 (1). Here, we report the design of new inhibitors based on the crystal structure of ATX in complex with inhibitor 1. Furthermore, we describe the syntheses and activities of these new inhibitors, whose potencies can be explained by structural data. To understand the difference in activity between two different isomers with nanomolar potencies, we performed molecular docking experiments. Intriguingly, molecular docking suggested a remarkable binding pose for one of the isomers, which differs from the original binding pose of inhibitor 1 for ATX, opening further options for inhibitor design.