diethyl <methyl>phosphonate | 163223-13-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl <methyl>phosphonate
• 英文别名: diethyl ((ethoxy(5-hydroxypentyl)phosphinoyl)methyl)phosphonate；5-[Diethoxyphosphorylmethyl(ethoxy)phosphoryl]pentan-1-ol
• CAS: 163223-13-0
• 化学式: C₁₂H₂₈O₆P₂
• 分子量: 330.298
• InChiKey: DPXFTHYTLVYCHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲基磺酰氯 、 diethyl <methyl>phosphonate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以54%的产率得到diethyl <pentyl>phosphinoyl>methyl>phosphonate
  参考文献：
  名称：

  [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase

  摘要：

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.

  DOI：

  10.1021/jm00006a020
• 作为产物：
  描述：

  diethyl <methyl>phosphonate 在 sodium hydroxide 、 硼烷 、 双氧水 作用下， 生成 diethyl <methyl>phosphonate
  参考文献：
  名称：

  [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase

  摘要：

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.

  DOI：

  10.1021/jm00006a020

文献信息

• Heterocyclic compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0478292A1

  公开（公告）日：1992-04-01

  Compounds of the formula (I): or a pharmaceutically acceptable salt or ester thereof, wherein X¹, is nitrogen or a group CH and X² is nitrogen or a group CR⁵ wherein R⁵ is hydrogen, hydroxy, halo or a group NHR⁶ wherein R⁶ is hydrogen or a C₁₋₄ alkyl or C₁₋₄ alkylcarbonyl group, R¹ is amino or hydrogen; R² is hydrogen, halo, SH, a group NHR⁷ wherein R⁷ is hydrogen or a C₁₋₄ alkyl or C₁₋₄ alkylcarbonyl group or R² is a group OR⁸ wherein R⁸ is hydrogen, C₁₋₄ alkyl or benzyl, R³ and R⁴ are the same or different and each is hydrogen or halo, X³ is a chain containing m CH₂ groups and n oxygen atoms, m being 1, 2, 3, 4, or 5 and n being 0, 1 or 2 the sum of m and n being 2, 3, 4, 5, or 6; are disclosed as inhibitors of the enzyme, purine nucleoside phosphorylase, pharmaceutical compositions containing the compounds, their use in medicine and processes for their preparation are also described.

  式(I)的化合物或其医药上可接受的盐或酯，其中X¹为氮或CH基团，X²为氮或CR⁵基团，其中R⁵为氢、羟基、卤素或NHR⁶基团，其中R⁶为氢或C₁₋₄烷基或C₁₋₄烷基羰基基团，R¹为氨基或氢；R²为氢、卤素、SH、NHR⁷基团，其中R⁷为氢或C₁₋₄烷基或C₁₋₄烷基羰基基团，或R²为OR⁸基团，其中R⁸为氢、C₁₋₄烷基或苄基，R³和R⁴相同或不同，均为氢或卤素，X³为含有m个CH₂基团和n个氧原子的链，其中m为1、2、3、4或5，n为0、1或2，m和n的总和为2、3、4、5或6；作为嘌呤核苷酸磷酸化酶的抑制剂进行了披露，还描述了含有该化合物的制药组合物、它们在医学上的用途以及其制备方法。
• [[(Guaninylalkyl)phosphinico]methyl]phosphonic Acids. Multisubstrate Analog Inhibitors of Human Erythrocyte Purine Nucleoside Phosphorylase
  作者：James L. Kelley、Ed W. McLean、Ronald C. Crouch、Devron R. Averett、Joel V. Tuttle

  DOI：10.1021/jm00006a020

  日期：1995.3

  A series of [[(guaninylalkyl)phosphinico]methyl]phosphonic acids, 2, was synthesized and tested as inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). The target (phosphinicomethyl)phosphonic acids 2 were synthesized in six or seven steps from alkenylphosphonates 4. The latter were converted to the intermediate alkylmesylates 9 in a series of steps that included (1) conversion of the diethyl phosphonates 4 to the (phosphinoylmethyl)pho sphonates 7 and (2) conversion of the terminal double bond of [(alkenylphosphinoyl)methyl]-phosphonates 7 to the alkylmesylates 9. The pure 9-isomers 2 were obtained by alkylation of 2-amino-6-(2-methoxyethoxy)-9H-purine with alkylmesylates 9 followed by hydrolysis of the protecting groups with concentrated hydrochloric acid and ion exchange chromatography to give 2 as hydrated ammonium salts. The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)pentyl]phosphinico]methyl]phosphonic acid(2b), was a multisubstrate analogue inhibitor with a K-i' of 3.1 nM. Optimum PNPase inhibitory activity required the presence of zinc ions in the assay medium. These potent inhibitors of PNPase exhibited only weak activity against human leukemic T-cells in vitro.