ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate | 892663-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate
• 英文别名: Ethyl 6-(5-chloro-2-((4-chloro-2-fluorobenzyl)oxy)benzyl)picolinate；ethyl 6-[[5-chloro-2-[(4-chloro-2-fluorophenyl)methoxy]phenyl]methyl]pyridine-2-carboxylate
• CAS: 892663-09-1
• 化学式: C₂₂H₁₈Cl₂FNO₃
• 分子量: 434.294
• InChiKey: WGOSUQFHQDEFND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate 在 sodium thiomethoxide 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以76%的产率得到6-[(5-chloro-2-hydroxyphenyl)methyl]-2-pyridinecarboxylic acid
  参考文献：
  名称：

  WO2006/66968

  摘要：

  公开号：
• 作为产物：
  描述：

  4-氯-2-碘苯甲醚, 在 tris-(dibenzylideneacetone)dipalladium(0) 、 异丙基氯化镁 、 三溴化硼 、 potassium carbonate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 4.0h， 生成 ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate
  参考文献：
  名称：

  Selection and Development of the Manufacturing Route for EP₁ Antagonist GSK269984B

  摘要：

  A potential manufacturing route for the EP1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed. This route utilised a phenolic aldol reaction as the key step and relied on selective hydrogenolysis to reduce an intermediate diarylmethanol. Further optimisation of the selected route is presented, delivering GSK269984B in three stages and 46% overall yield from readily available starting materials.

  DOI：

  10.1021/op100072y

文献信息

• Pyridine Compounds For The Treatment Of Prostaglandin Mediated Diseases
  申请人：Martin Paul Giblin Gerard

  公开号：US20080249138A1

  公开（公告）日：2008-10-09

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein X, Y, Z, R 2a , R 2b , R 3a , R 3b , R 8 , R 9 , and R x are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  化合物的化学式为（I）或其药学上可接受的衍生物： 其中X、Y、Z、R2a、R2b、R3a、R3b、R8、R9和Rx如规范所定义，制备这种化合物的过程，包含这种化合物的药物组合物以及在医学上使用这种化合物。
• PYRIDYL COMPOUNDS
  申请人：Giblin Gerard Martin Paul

  公开号：US20090099177A1

  公开（公告）日：2009-04-16

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein R 1 , and R 2 , and R 3 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  化合物的公式(I)或其药学上可接受的衍生物：其中R1，R2和R3如规范所定义，制备这种化合物的过程，包括这种化合物的药物组合物以及这种化合物在医学上的使用。
• Pyridine compounds for the treatment of prostaglandin mediated diseases
  申请人：Glaxo Group Limited

  公开号：US07759369B2

  公开（公告）日：2010-07-20

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein X, Y, Z, R2a, R2b, R3a, R3b, R8, R9, and Rx are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  化合物的公式(I)或其药学上可接受的衍生物：其中X、Y、Z、R2a、R2b、R3a、R3b、R8、R9和Rx的定义如规范所述，制备这种化合物的过程，包括这种化合物的药物组合物以及这种化合物在医学上的用途。
• WO2007/128752
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP1 receptor antagonist for the treatment of inflammatory pain
  作者：Adrian Hall、Andy Billinton、Susan H. Brown、Anita Chowdhury、Nicholas M. Clayton、Gerard M.P. Giblin、Mairi Gibson、Paul A. Goldsmith、David N. Hurst、Alan Naylor、Caroline F. Peet、Tiziana Scoccitti、Alexander W. Wilson、Wendy Winchester

  DOI：10.1016/j.bmcl.2009.02.112

  日期：2009.5

  We describe the medicinal chemistry programme that led to the identification of the EP1 receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP1 antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic pro. ling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study. (C) 2009 Elsevier Ltd. All rights reserved.