5-{(Z)-1-[4-(benzyloxy)-3-methoxyphenyl]methylidene}-3-(4-fluorobenzyl)-1,3-thiazolane-2,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-{(Z)-1-[4-(benzyloxy)-3-methoxyphenyl]methylidene}-3-(4-fluorobenzyl)-1,3-thiazolane-2,4-dione
• 英文别名: (5Z)-5-[4-(benzyloxy)-3-methoxybenzylidene]-3-(4-fluorobenzyl)-1,3-thiazolidine-2,4-dione；(5Z)-3-[(4-fluorophenyl)methyl]-5-[(3-methoxy-4-phenylmethoxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₂₅H₂₀FNO₄S
• 分子量: 449.503
• InChiKey: BMEZXIZUIMZICR-UCQKPKSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 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：
  81.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-[(4-benzyloxy-3-methoxyphenyl)methylidene]-2,4-thiazolidinedione 、 4-氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以97%的产率得到5-{(Z)-1-[4-(benzyloxy)-3-methoxyphenyl]methylidene}-3-(4-fluorobenzyl)-1,3-thiazolane-2,4-dione
  参考文献：
  名称：

  Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin

  摘要：

  Autotaxin (ATX) is an extracellular enzyme that hydrolyzes lysophosphatidylcholine (LPC) to produce the lipid mediator lysophosphatidic acid (LPA). The ATX LPA signaling axis has been implicated in diverse physiological and pathological processes, including vascular development, inflammation, fibrotic disease, and tumor progression. Therefore targeting ATX with small molecule inhibitors is an attractive therapeutic strategy. We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optimization of boronic acid based ATX inhibitors. The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC50 = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use.

  DOI：

  10.1021/jm1005012

文献信息

• Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin
  作者：Harald M. H. G. Albers、Laurens A. van Meeteren、David A. Egan、Erica W. van Tilburg、Wouter H. Moolenaar、Huib Ovaa

  DOI：10.1021/jm1005012

  日期：2010.7.8

  Autotaxin (ATX) is an extracellular enzyme that hydrolyzes lysophosphatidylcholine (LPC) to produce the lipid mediator lysophosphatidic acid (LPA). The ATX LPA signaling axis has been implicated in diverse physiological and pathological processes, including vascular development, inflammation, fibrotic disease, and tumor progression. Therefore targeting ATX with small molecule inhibitors is an attractive therapeutic strategy. We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optimization of boronic acid based ATX inhibitors. The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC50 = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use.