diethyl 2-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoyl]methyl-phosphonate | 1256241-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: diethyl 2-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoyl]methyl-phosphonate
• 英文别名: N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-2-diethoxyphosphorylacetamide
• CAS: 1256241-49-2
• 化学式: C₁₂H₁₉N₂O₅PS
• 分子量: 334.333
• InChiKey: SBEXIARDOMIHHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoyl]methyl-phosphonate 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 disodium 2-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoyl]methylphosphonate
  参考文献：
  名称：

  Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors

  摘要：

  The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.062
• 作为产物：
  描述：

  5-乙酰基-2-氨基-4-甲基噻唑 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 diethyl 2-[(5-acetyl-4-methyl-1,3-thiazol-2-yl)carbamoyl]methyl-phosphonate
  参考文献：
  名称：

  Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors

  摘要：

  The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.062

文献信息

• 31P NMR kinetic study of the tandem cleavage of phosphonate esters by bromotrimethylsilane
  作者：Anne C. Conibear、Kevin A. Lobb、Perry T. Kaye

  DOI：10.1016/j.tet.2010.08.058

  日期：2010.10

  1H and 31P NMR methods have been used to access rate constants and activation parameters for each of the consecutive second-order silylation reactions involved in the overall transformation (1a→3a→4a), while computational optimisation of the rate constants obtained from the initial, linear phase of each reaction has permitted an excellent fit with the experimental data for the entire course of the

  1 H和31 P NMR方法已用于访问参与整体转化（1a → 3a → 4a）的每个连续二阶甲硅烷基化反应的速率常数和活化参数，同时对从每个反应的初始线性阶段都非常适合整个反应过程的实验数据。
• Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors
  作者：Taryn Bodill、Anne C. Conibear、Gregory L. Blatch、Kevin A. Lobb、Perry T. Kaye

  DOI：10.1016/j.bmc.2010.11.062

  日期：2011.2

  The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design. (C) 2010 Elsevier Ltd. All rights reserved.
• Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
  作者：Taryn Bodill、Anne C. Conibear、Marius K.M. Mutorwa、Jessica L. Goble、Gregory L. Blatch、Kevin A. Lobb、Rosalyn Klein、Perry T. Kaye

  DOI：10.1016/j.bmc.2013.04.076

  日期：2013.7

  DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. (C) 2013 Elsevier Ltd. All rights reserved.