diethyl [N-(3-hydroxyphenyl)carbamoyl]methylphosphonate | 1182347-19-8

• 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: diethyl [N-(3-hydroxyphenyl)carbamoyl]methylphosphonate
• 英文别名: 2-diethoxyphosphoryl-N-(3-hydroxyphenyl)acetamide
• CAS: 1182347-19-8
• 化学式: C₁₂H₁₈NO₅P
• 分子量: 287.252
• InChiKey: RAYYAQPAZGFTIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl [N-(3-hydroxyphenyl)carbamoyl]methylphosphonate 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以88%的产率得到N-[3-[tert-butyl(dimethyl)silyl]oxyphenyl]-2-diethoxyphosphorylacetamide
  参考文献：
  名称：

  N-苄基化的（N-芳基氨基甲酰基）烷基膦酸衍生物的合成和抗疟活性。

  摘要：

  已经制备了一系列新颖且易于获得的N-苄基化（N-芳基氨基甲酰基）烷基膦酸酯和相关化合物作为潜在的抗疟剂。生物测定法表明，这些化合物中的一些对恶性疟原虫表现出有希望的活性，并且对HeLa细胞没有明显的生长抑制作用。

  DOI：

  10.1016/j.bmc.2016.04.021
• 作为产物：
  描述：

  3-氨基苯酚 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 diethyl [N-(3-hydroxyphenyl)carbamoyl]methylphosphonate
  参考文献：
  名称：

  Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.04.076

文献信息

• Synthesis and anti-parasitic activity of C -benzylated ( N -arylcarbamoyl)alkylphosphonate esters
  作者：Christiana M. Adeyemi、Michelle Isaacs、Dumisani Mnkandhla、Rosalyn Klein、Heinrich C. Hoppe、Rui W.M. Krause、Kevin A. Lobb、Perry T. Kaye

  DOI：10.1016/j.tet.2017.01.045

  日期：2017.3

  C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.

  解决了C-苄基化（N-芳基氨基甲酰基）膦酸酯合成中意外的依赖于取代基的区域选择性挑战。所述Ç -benzylated Ñ -furfurylcarbamoyl衍生物显示出低微摩尔Pf的LDH抑制，而之一Ç -benzylated Ñ -arylcarbamoyl类似物反对那加那活性布氏锥虫寄生虫其负责在牛非洲锥虫病。
• 3-Substituted Anilines as Scaffolds for the Construction of Glutamine Synthetase and DXP-Reductoisomerase Inhibitors
  作者：Marius Mutorwa、Sheriff Salisu、Gregory L. Blatch、Colin Kenyon、Perry T. Kaye

  DOI：10.1080/00397910802663444

  日期：2009.7.7

  Access to a series of truncated ATP analogs, as potential anti-tuberculosis agents, has been explored via alkylation and acylation of 3-aminophenol, whereas chloroacetylation, using chloroacetyl chloride, and subsequent Arbuzov phosphonation of a series of 3-substituted anilines have afforded a series of phosphonate derivatives as potential antimalarial agents.
• 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.
• Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives
  作者：Christiana M. Adeyemi、Faridoon、Michelle Isaacs、Dumisani Mnkandhla、Heinrich C. Hoppe、Rui W.M. Krause、Perry T. Kaye

  DOI：10.1016/j.bmc.2016.04.021

  日期：2016.12

  A series of novel and readily accessible N-benzylated (N-arylcarbamoyl)alkylphosphonate esters and related compounds have been prepared as potential antimalarial agents. Bioassays reveal that some of these compounds exhibit promising activity against Plasmodium falciparum, and exhibit no significant growth inhibition of HeLa cells.

  已经制备了一系列新颖且易于获得的N-苄基化（N-芳基氨基甲酰基）烷基膦酸酯和相关化合物作为潜在的抗疟剂。生物测定法表明，这些化合物中的一些对恶性疟原虫表现出有希望的活性，并且对HeLa细胞没有明显的生长抑制作用。