methanesulfonic acid 4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl ester | 477585-18-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methanesulfonic acid 4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl ester
• 英文别名: (4-methoxy-3,5-dimethylpyridin-2-yl)methyl methanesulfonate；4-Methoxy-3,5-dimethyl-2-pyridinemethanol 2-methanesulfonate
• CAS: 477585-18-5
• 化学式: C₁₀H₁₅NO₄S
• 分子量: 245.299
• InChiKey: ILAOPYLMWIYNTF-UHFFFAOYSA-N

物化性质

• 沸点：
  413.2±45.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.18
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.49
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl ester 在 sodium tetrahydroborate 、 正丁基锂 、 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 5.0h， 生成 {3-eicosanoylamino-2-hydroxy-4-[4-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethoxy)-phenyl]-butyl}-phosphonic acid dimethyl ester
  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：

  4-甲氧基-3,5-二甲基-2-羟甲基吡啶 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 methanesulfonic acid 4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl ester
  参考文献：
  名称：

  使用生物正交化学指导Siglec-唾液酸在活细胞上的相互作用

  摘要：

  终止细胞表面聚糖的唾液酸糖形成唾液酸结合免疫球蛋白样凝集素（Siglec）家族的配体，后者是免疫细胞表达的免疫调节受体。唾液酸和Siglecs之间的相互作用调节免疫系统，而像差则导致自身免疫和癌症等病理。由于缺乏特定的工具，很难研究活细胞之间的唾液酸/ Siglec相互作用。在这里，我们报告了一种糖工程方法来重塑唾液酸的活细胞及其与Siglecs的结合。使用生物正交化学，产生了具有六十多种不同唾液酸修饰的细胞文库，该文库显示出与不同Siglec家族成员的结合显着增加。合理的设计降低了交叉反应性，并导致发现了三种选择性Siglec-5 / 14配体。此外，携带针对Siglec-3的唾液酸配体的糖工程细胞抑制了Siglec-3的活化+单核细胞通过NF-κB和IRF途径。

  DOI：

  10.1002/anie.201612193

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.