methyl 2-(4-hydroxy-3-methoxyphenyl)-2-oxoacetate | 1208246-43-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: methyl 2-(4-hydroxy-3-methoxyphenyl)-2-oxoacetate
• 英文别名: Vanillic acid methyl ester；4-hydroxy-3-methoxyphenylglyoxylic acid methyl ester；Carbomethoxyvanillin
• CAS: 1208246-43-8
• 化学式: C₁₀H₁₀O₅
• 分子量: 210.186
• InChiKey: PVRDAVSDHWPSOF-UHFFFAOYSA-N

物化性质

• 沸点：
  369.5±32.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-hydroxy-3-methoxyphenyl)-2-oxoacetate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以72%的产率得到2-(4-羟基-3-甲氧基苯基)-2-氧代乙酸
  参考文献：
  名称：

  Structure–activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene

  摘要：

  The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversely, only a modest erosion of activity was observed upon a-methylation and alpha-methylenation of the side chain. Surprisingly, introduction of an iodine atom in the guaiacyl moiety of the oxygen isoster 2h led to an unexpected and remarkable (> 1000-fold) increase of potency, affording 2i, a compound that outperforms RTX in terms of vanilloid agonism and represents the first one-digit picomolar ligand of a TRP channel discovered to date. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.035
• 作为产物：
  描述：

  methyl vanillmandelate 在 Jones reagent 作用下， 生成 methyl 2-(4-hydroxy-3-methoxyphenyl)-2-oxoacetate
  参考文献：
  名称：

  Structure–activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene

  摘要：

  The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversely, only a modest erosion of activity was observed upon a-methylation and alpha-methylenation of the side chain. Surprisingly, introduction of an iodine atom in the guaiacyl moiety of the oxygen isoster 2h led to an unexpected and remarkable (> 1000-fold) increase of potency, affording 2i, a compound that outperforms RTX in terms of vanilloid agonism and represents the first one-digit picomolar ligand of a TRP channel discovered to date. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.035

文献信息

• Synthesis of novel non-cross-linking pyrrolobenzodiazepines with remarkable DNA binding affinity and potent antitumour activity
  作者：Ahmed Kamal、N. Laxman、G. Ramesh、K. Neelima、Anand K. Kondapi

  DOI：10.1039/b009195m

  日期：——

  Mixed imine–amide pyrrolobenzodiazepine dimers have been prepared which exhibit potent antitumour activity and have significant DNA binding affinity; one of them, 1c, has been shown to cause a remarkable rise in the melting temperature of calf thymus DNA.

  已经制备出混合亚胺-酰胺吡咯并苯二氮杂环二聚体，这些化合物表现出强大的抗肿瘤活性和显著的DNA结合亲和力；其中一个化合物1c已被证明能显著提高小牛胸腺DNA的熔融温度。
• Structure–activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene
  作者：Giovanni Appendino、Abdellah Ech-Chahad、Alberto Minassi、Luciano De Petrocellis、Vincenzo Di Marzo

  DOI：10.1016/j.bmcl.2009.11.035

  日期：2010.1

  The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversely, only a modest erosion of activity was observed upon a-methylation and alpha-methylenation of the side chain. Surprisingly, introduction of an iodine atom in the guaiacyl moiety of the oxygen isoster 2h led to an unexpected and remarkable (> 1000-fold) increase of potency, affording 2i, a compound that outperforms RTX in terms of vanilloid agonism and represents the first one-digit picomolar ligand of a TRP channel discovered to date. (C) 2009 Elsevier Ltd. All rights reserved.