B-[4-[[4-[(Z)-[3-[(4-氟苯基)甲基]-2,4-二氧代-5-噻唑烷亚基]甲基]苯氧基]甲基]苯基]硼酸 | 1312201-00-5

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: B-[4-[[4-[(Z)-[3-[(4-氟苯基)甲基]-2,4-二氧代-5-噻唑烷亚基]甲基]苯氧基]甲基]苯基]硼酸
• 英文名称: (Z)-(4-((4-((3-(4-fluorobenzyl)-2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid
• 英文别名: [4-[[4-[(Z)-[3-[(4-fluorophenyl)methyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy]methyl]phenyl]boronic acid；HA155；(Z)-4-[(4-{[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolan-5-yliden]methyl}phenoxy)methyl]benzene boronic acid
• CAS: 1312201-00-5
• 化学式: C₂₄H₁₉BFNO₅S
• 分子量: 463.294
• InChiKey: BRWUZCBSWABPMR-XKZIYDEJSA-N

物化性质

• 溶解度：
  DMSO：可溶10mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  7

制备方法与用途

生物活性

HA-155 是一种高效、选择性的 ATX 抑制剂，其 IC50 值为 5.7 nM。

靶点

IC50: 5.7 nM (ATX)

体外研究

HA-155 通过结合到 ATX 活性位点来抑制 ATX。此外，它以剂量依赖的方式完全阻断了凝血酶介导的血小板衍生 LPA 增加。

反应信息

• 作为反应物：
  描述：

  B-[4-[[4-[(Z)-[3-[(4-氟苯基)甲基]-2,4-二氧代-5-噻唑烷亚基]甲基]苯氧基]甲基]苯基]硼酸 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以77%的产率得到(4-((4-((3-(4-fluorobenzyl)-2,4-dioxothiazolidin-5-yl)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
• 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 B-[4-[[4-[(Z)-[3-[(4-氟苯基)甲基]-2,4-二氧代-5-噻唑烷亚基]甲基]苯氧基]甲基]苯基]硼酸
  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.