4-((3-aminophenyl)ethynyl)-2-(3,4-dichlorobenzylthio)benzoic acid | 1336982-67-2

• 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: 4-((3-aminophenyl)ethynyl)-2-(3,4-dichlorobenzylthio)benzoic acid
• 英文别名: 4-[2-(3-Aminophenyl)ethynyl]-2-[(3,4-dichlorophenyl)methylsulfanyl]benzoic acid
• CAS: 1336982-67-2
• 化学式: C₂₂H₁₅Cl₂NO₂S
• 分子量: 428.339
• InChiKey: VOKUNEUMASWNEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((3-aminophenyl)ethynyl)-2-(3,4-dichlorobenzylthio)benzoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 4-((3-(2-aminoacetamido)phenyl)ethynyl)-2-(3,4-dichlorobenzylthio)benzoic acid trifluoroacetate
  参考文献：
  名称：

  Small Molecule Receptor Protein Tyrosine Phosphatase γ (RPTPγ) Ligands That Inhibit Phosphatase Activity via Perturbation of the Tryptophan–Proline–Aspartate (WPD) Loop

  摘要：

  Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase gamma (RPTP gamma) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTP gamma, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.

  DOI：

  10.1021/jm2003766
• 作为产物：
  描述：

  4-溴-2-疏基苯甲酸 在 copper(l) iodide 、 四(三苯基膦)钯 、 sodium methylate 、 三乙胺 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 7.5h， 生成 4-((3-aminophenyl)ethynyl)-2-(3,4-dichlorobenzylthio)benzoic acid
  参考文献：
  名称：

  Small Molecule Receptor Protein Tyrosine Phosphatase γ (RPTPγ) Ligands That Inhibit Phosphatase Activity via Perturbation of the Tryptophan–Proline–Aspartate (WPD) Loop

  摘要：

  Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase gamma (RPTP gamma) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTP gamma, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.

  DOI：

  10.1021/jm2003766

文献信息

• Small Molecule Receptor Protein Tyrosine Phosphatase γ (RPTPγ) Ligands That Inhibit Phosphatase Activity via Perturbation of the Tryptophan–Proline–Aspartate (WPD) Loop
  作者：Steven Sheriff、Brett R. Beno、Weixu Zhai、Walter A. Kostich、Patricia A. McDonnell、Kevin Kish、Valentina Goldfarb、Mian Gao、Susan E. Kiefer、Joseph Yanchunas、Yanling Huang、Shuhao Shi、Shirong Zhu、Carolyn Dzierba、Joanne Bronson、John E. Macor、Kingsley K. Appiah、Ryan S. Westphal、Jonathan O’Connell、Samuel W. Gerritz

  DOI：10.1021/jm2003766

  日期：2011.10.13

  Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase gamma (RPTP gamma) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTP gamma, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.