(2,3,4-trimethoxy-phenyl)-glyoxylic acid | 103988-63-2

• 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: (2,3,4-trimethoxy-phenyl)-glyoxylic acid
• 英文别名: (2,3,4-Trimethoxy-phenyl)-glyoxylsaeure；2,3,4-Trimethoxybenzoylformic acid；2-oxo-2-(2,3,4-trimethoxyphenyl)acetic acid
• CAS: 103988-63-2
• 化学式: C₁₁H₁₂O₆
• mdl: MFCD12439940
• 分子量: 240.213
• InChiKey: LGNZGLPVASKSLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2,3,4-trimethoxy-phenyl)-glyoxylic acid 在 ammonium acetate 、 溶剂黄146 、 N,N'-羰基二咪唑 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 反应 0.07h， 生成 5-(1H-indol-3-yl)-3-(2,3,4-trimethoxyphenyl)-1H-pyrazin-2-one
  参考文献：
  名称：

  Optimization of Potent DFG-in Inhibitors of Platelet Derived Growth Factor Receptorβ (PDGF-Rβ) Guided by Water Thermodynamics

  摘要：

  In this study we report on the hit optimization of substituted 3,5-diaryl-pyrazin-2(1H)-ones toward potent and effective platelet-derived growth factor receptor (PDGF-R) beta-inhibitors. Originally, the 3,5-diaryl-pyrazin-2-one core was derived from the marine sponge alkaloid family of hamacanthins. In our first series compound 2 was discovered as a promising hit showing strong activity against PDGF-R beta in the kinase assay (IC50 = 0.5 mu M). Furthermore, 2 was shown to be selective for PDGF-R beta in a panel of 24 therapeutically relevant protein kinases. Molecular modeling studies on a PDGF-R beta homology model using prediction of water thermodynamics suggested an optimization strategy for the 3,5-diaryl-pyrazin-2-ones as DFG-in binders by using a phenolic OH function to replace a structural water molecule in the ATP binding site. Indeed, we identified compound 38 as a highly potent inhibitor with an IC50 value of 0.02 mu M in a PDGF-R beta enzymatic assay also showing activity against PDGF-R dependent cancer cells.

  DOI：

  10.1021/jm500373x
• 作为产物：
  描述：

  (2,3,4-trimethoxy-phenyl)-glyoxylonitrile 在 盐酸 作用下， 生成 (2,3,4-trimethoxy-phenyl)-glyoxylic acid
  参考文献：
  名称：

  Mauthner, Chemische Berichte, 1909, vol. 42, p. 194

  摘要：

  DOI：

文献信息

• Silver-catalyzed decarboxylative cyclization for the synthesis of substituted pyrazoles from 1,2-diaza-1,3-dienes and α-keto acids
  作者：Sarita Katiyar、Abhishek Kumar、Koneni V. Sashidhara

  DOI：10.1039/d2cc01793h

  日期：——

  A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles were well prepared in moderate to good yields. In addition, the synthetic utility of this protocol has been demonstrated by synthesizing analogs of

  已经开发了一种银催化的脱羧环化方法，用于从容易获得的 1,2-二氮杂-1,3-二烯和 α-酮酸合成取代的吡唑。在优化的条件下，一系列多取代吡唑以中等至良好的收率很好地制备。此外，该协议的合成效用已通过合成 FDA 批准的药物（如抗炎药、lonazolac 和抗肥胖药物 rimonabant）的类似物得到证明。
• Kuroda; Nakamura, Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1932, vol. 18, p. 61,78
  作者：Kuroda、Nakamura

  DOI：——

  日期：——
• Hargreaves et al., Journal of Applied Chemistry, 1958, vol. 8, p. 273,280
  作者：Hargreaves et al.

  DOI：——

  日期：——
• PIPERIDINE AND PYRROLIDINE DERIVATIVES DISPLAYING NEURONAL ACTIVITY
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1204657A1

  公开（公告）日：2002-05-15
• [EN] PIPERIDINE AND PYRROLIDINE DERIVATIVES DISPLAYING NEURONAL ACTIVITY<br/>[FR] DERIVES DE PIPERIDINE ET DE PYRROLIDINE AYANT UNE ACTIVITE NEURONALE
  申请人：SCHERING AG

  公开号：WO2001012622A1

  公开（公告）日：2001-02-22

  The invention relates to the compounds of Formula (I), as well as the process for their production and their use as pharmaceutical agents.