diethyl [2-(3-methoxyphenylamino)-2-oxoethyl]phosphonate | 803686-21-7

• 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 [2-(3-methoxyphenylamino)-2-oxoethyl]phosphonate
• 英文别名: 2-diethoxyphosphoryl-N-(3-methoxyphenyl)acetamide
• CAS: 803686-21-7
• 化学式: C₁₃H₂₀NO₅P
• 分子量: 301.279
• InChiKey: RUHCALISRLXHIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl [2-(3-methoxyphenylamino)-2-oxoethyl]phosphonate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (E)-4-{2-[2-(4-methoxyphenylcarbamoyl)-1-methylvinyl]benzofuran-7-yloxy}butyric acid
  参考文献：
  名称：

  Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity

  摘要：

  合成了变种的苯并[b]呋喃衍生物，这些衍生物在2、4和5位含有(E)-和(Z)-2-烷基氨基甲酰基-1-甲基乙烯基基团，而在7位则含有羧丙氧基或(1-苯基)乙氧基基团，以寻找新型的选择性白三烯B4（LTB4）受体拮抗剂。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(4v)对人类BLT2受体(hBLT2)表现出选择性抑制作用。另一方面，(E)-2-乙酰基-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(7v)则同时抑制人类BLT1受体(hBLT1)和hBLT2。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团大致位于苯并[b]呋喃环的同一平面上，而(E)-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团与苯并[b]呋喃环平面之间的扭转角度为45.7°。然而，(Z)-(2-烷基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃表现出不活性。抑制活性取决于2-二乙基氨基甲酰基-1-甲基乙烯基基团的构象。

  DOI：

  10.1039/b503615a
• 作为产物：
  描述：

  间氨基苯甲醚 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 diethyl [2-(3-methoxyphenylamino)-2-oxoethyl]phosphonate
  参考文献：
  名称：

  Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity

  摘要：

  合成了变种的苯并[b]呋喃衍生物，这些衍生物在2、4和5位含有(E)-和(Z)-2-烷基氨基甲酰基-1-甲基乙烯基基团，而在7位则含有羧丙氧基或(1-苯基)乙氧基基团，以寻找新型的选择性白三烯B4（LTB4）受体拮抗剂。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(4v)对人类BLT2受体(hBLT2)表现出选择性抑制作用。另一方面，(E)-2-乙酰基-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(7v)则同时抑制人类BLT1受体(hBLT1)和hBLT2。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团大致位于苯并[b]呋喃环的同一平面上，而(E)-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团与苯并[b]呋喃环平面之间的扭转角度为45.7°。然而，(Z)-(2-烷基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃表现出不活性。抑制活性取决于2-二乙基氨基甲酰基-1-甲基乙烯基基团的构象。

  DOI：

  10.1039/b503615a

文献信息

• Preparation of 2-, 3-, 4- and 7-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans and their BLT₁and/or BLT₂inhibitory activities
  作者：Kumiko Ando、Yoko Kawamura、Yukiko Akai、Jun-ichi Kunitomo、Takehiko Yokomizo、Masayuki Yamashita、Shunsaku Ohta、Takahiro Ohishi、Yoshitaka Ohishi

  DOI：10.1039/b710935k

  日期：——

  Several 2-alkylcarbamoyl-1-alkylvinylbenzo[b]furans were designed to find a selective leukotriene B4 (LTB4) receptor antagonist. 2-(2-Alkylcarbamoyl-1-alkylvinyl)benzo[b]furans having a substituent group at the 3-position, 4-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans having a substituent group at the 3-position, and 7-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans and 3-(2-alkylcarbamoyl-1-alkylvinyl)benzo[b]furans were prepared and evaluated for LTB4receptor (BLT1 and BLT2) inhibitory activities. (E)-3-Amino-4-[2-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]-1-methylvinyl]benzo[b]furan ((E)-17c) showed potent and selective inhibitory activity for BLT2. On the other hand, (E)-7-(2-diethylcarbamoyl-1-methylvinyl)benzo[b]furan ((E)-27a) showed potent inhibitory activity for both BLT1 and BLT2.

  设计了几种2-烷基氨基甲酰基-1-烷基乙烯基苯并[b]呋喃，旨在寻找选择性的白三烯B4（LTB4）受体拮抗剂。合成了在3-位具有取代基的2-(2-烷基氨基甲酰基-1-烷基乙烯基)苯并[b]呋喃、在3-位具有取代基的4-(2-烷基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃、7-(2-烷基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃和3-(2-烷基氨基甲酰基-1-烷基乙烯基)苯并[b]呋喃，并评估了它们对LTB4受体（BLT1和BLT2）的抑制活性。(E)-3-氨基-4-[2-[2-(3,4-二甲氧基苯基)乙基氨基甲酰基]-1-甲基乙烯基]苯并[b]呋喃((E)-17c)显示出对BLT2具有强效且选择性的抑制活性。另一方面，(E)-7-(2-二乙基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃((E)-27a)对BLT1和BLT2均显示出强效的抑制活性。
• Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity
  作者：Yukako Tabuchi、Yuko Ando、Hidemi Kanemura、Ikuo Kawasaki、Takahiro Ohishi、Masao Koida、Ryo Fukuyama、Hiromichi Nakamuta、Shunsaku Ohta、Kiyoharu Nishide、Yoshitaka Ohishi

  DOI：10.1016/j.bmc.2009.04.017

  日期：2009.6

  mixture of (E)- and (Z)-(E)-2-aralkenylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo-formylmethylene group on the oxazine ring. The Z-isomer was more stable than the E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two different conditions to obtain various butadiene derivatives (12) containing benzo[b]furo[3,2-d][1,3]oxazine skeleton

  2-乙酰基-3-酰基氨基苯并[ b ]呋喃 ( 9d – o ) 与 Vilsmeier (VM) 试剂反应得到 ( E )- 和 ( Z )-( E )-2-芳烯基苯并 [ b ]furo的混合物[3,2- d ][1,3]oxazin-4-ylidene}乙醛 ( 5 )，在恶嗪环上具有特征性的外-甲酰基亚甲基。Z-异构体比E-异构体更稳定。Z-异构体（（Z）-5）在两种不同的条件下与膦酸酯试剂反应，得到各种丁二烯衍生物（12 ) 含有苯并[ b ]呋喃[3,2- d ][1,3]恶嗪骨架。评价了典型化合物（5和12）的抗破骨性骨吸收活性、对 cysLT1 受体的拮抗活性和对 MIA PaCa-2 和 MCF-7 的生长抑制活性。化合物12f和12j显示出与 E 2 (17β-雌二醇)相当的有效抗破骨性骨吸收活性。
• 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 of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity
  作者：Kumiko Ando、Eriko Tsuji、Yuko Ando、Jun-ichi Kunitomo、Reina Kobayashi、Takehiko Yokomizo、Takao Shimizu、Masayuki Yamashita、Shunsaku Ohta、Takeshi Nabe、Shigekatsu Kohno、Yoshitaka Ohishi

  DOI：10.1039/b503615a

  日期：——

  Variable benzo[b]furan derivatives having (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4- and 5-positions and a carboxylpropoxy or (1-phenyl)ethoxy group at the 7-position were prepared to find novel and selective leukotriene B4 (LTB4) receptor antagonists. (E)-2-(2-Diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition to the human BLT2 receptor (hBLT2). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7v) inhibited both human BLT1 receptor (hBLT1) and hBLT2. The (E)-2-(2-diethylcarbamoyl-1-methylvinyl) group lay on approximately the same plane as the benzo[b]furan ring, whereas the (E)-4-(2-diethylcarbamoyl-1-methylvinyl) group had the torsion angle (45.7°) from the benzo[b]furan ring plane. However, the (Z)-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans were inactive. The inhibitory activity depended on the conformation of the 2-diethylcarbamoyl-1-methylvinyl group.

  合成了变种的苯并[b]呋喃衍生物，这些衍生物在2、4和5位含有(E)-和(Z)-2-烷基氨基甲酰基-1-甲基乙烯基基团，而在7位则含有羧丙氧基或(1-苯基)乙氧基基团，以寻找新型的选择性白三烯B4（LTB4）受体拮抗剂。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(4v)对人类BLT2受体(hBLT2)表现出选择性抑制作用。另一方面，(E)-2-乙酰基-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)-7-(1-苯乙氧基)苯并[b]呋喃(7v)则同时抑制人类BLT1受体(hBLT1)和hBLT2。(E)-2-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团大致位于苯并[b]呋喃环的同一平面上，而(E)-4-(2-二乙基氨基甲酰基-1-甲基乙烯基)基团与苯并[b]呋喃环平面之间的扭转角度为45.7°。然而，(Z)-(2-烷基氨基甲酰基-1-甲基乙烯基)苯并[b]呋喃表现出不活性。抑制活性取决于2-二乙基氨基甲酰基-1-甲基乙烯基基团的构象。