dimethyl 2-[[[(3S)-3-acetamido-4-(ethylamino)-4-oxobutyl]-methoxyphosphoryl]methyl]pentanedioate | 1446694-03-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: dimethyl 2-[[[(3S)-3-acetamido-4-(ethylamino)-4-oxobutyl]-methoxyphosphoryl]methyl]pentanedioate
• CAS: 1446694-03-6
• 化学式: C₁₇H₃₁N₂O₈P
• 分子量: 422.415
• InChiKey: QQOKDKONLVGRLU-SHQYCYDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  28
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dimethyl 2-[[[(3S)-3-acetamido-4-(ethylamino)-4-oxobutyl]-methoxyphosphoryl]methyl]pentanedioate 在 sodium hydroxide 作用下， 反应 1.0h， 以91%的产率得到2-[[[(3S)-3-acetamido-4-(ethylamino)-4-oxobutyl]-hydroxyphosphoryl]methyl]pentanedioic acid
  参考文献：
  名称：

  Phosphinic acid-based inhibitors of tubulin polyglutamylases

  摘要：

  Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 mu M) and the most potent inhibitor displayed an IC50 value of 150 mu M. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.069
• 作为产物：
  描述：

  ((S)-4-(benzyloxy)-3-(((benzyloxy)carbonyl)amino)-4-oxobutyl)(5-methoxy-2-(methoxycarbonyl)-5-oxopentyl)phosphinic acid 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 三甲基硅烷化重氮甲烷 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 14.17h， 生成 dimethyl 2-[[[(3S)-3-acetamido-4-(ethylamino)-4-oxobutyl]-methoxyphosphoryl]methyl]pentanedioate
  参考文献：
  名称：

  Phosphinic acid-based inhibitors of tubulin polyglutamylases

  摘要：

  Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 mu M) and the most potent inhibitor displayed an IC50 value of 150 mu M. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.069

文献信息

• Phosphinic acid-based inhibitors of tubulin polyglutamylases
  作者：Yanjie Liu、Christopher P. Garnham、Antonina Roll-Mecak、Martin E. Tanner

  DOI：10.1016/j.bmcl.2013.05.069

  日期：2013.8

  Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 mu M) and the most potent inhibitor displayed an IC50 value of 150 mu M. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.