(S)-dimethyl 4-(4-((4-methoxy-3,5-dimethylpyridin-2-yl)methoxy)phenyl)-2-oxo-3-palmitamidobutylphosphonate | 935548-40-6

• 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: (S)-dimethyl 4-(4-((4-methoxy-3,5-dimethylpyridin-2-yl)methoxy)phenyl)-2-oxo-3-palmitamidobutylphosphonate
• CAS: 935548-40-6
• 化学式: C₃₇H₅₉N₂O₇P
• 分子量: 674.858
• InChiKey: WRLBXDPCYLOOLD-XIFFEERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.85
• 重原子数：
  47.0
• 可旋转键数：
  26.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  113.05
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (S)-dimethyl 4-(4-((4-methoxy-3,5-dimethylpyridin-2-yl)methoxy)phenyl)-2-oxo-3-palmitamidobutylphosphonate 在 三甲基溴硅烷 、 水 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 4.0h， 生成 {3-hexadecanoylamino-4-[4-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethoxy)-phenyl]-2-oxo-butyl}-phosphonic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors

  摘要：

  Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of P-keto and P-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.114
• 作为产物：
  描述：

  L-酪氨酸甲酯盐酸盐 在 正丁基锂 、 18-冠醚-6 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 (S)-dimethyl 4-(4-((4-methoxy-3,5-dimethylpyridin-2-yl)methoxy)phenyl)-2-oxo-3-palmitamidobutylphosphonate
  参考文献：
  名称：

  Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors

  摘要：

  Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of P-keto and P-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.114

文献信息

• α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors
  作者：Peng Cui、William F. McCalmont、Jose L. Tomsig、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmc.2007.11.078

  日期：2008.3

  Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two beta-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated alpha- and beta-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of beta-hydroxy phosphonates was also studied. Published by Elsevier Ltd.
• Synthesis and structure–activity relationships of tyrosine-based inhibitors of autotaxin (ATX)
  作者：James E. East、Andrew J. Kennedy、Jose L. Tomsig、Alexandra R. De Leon、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2010.09.030

  日期：2010.12

  Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA's role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX. (C) 2010 Elsevier Ltd. All rights reserved.