di-n-butyl methoxycarbonylphosphonate | 72304-81-5

• 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: di-n-butyl methoxycarbonylphosphonate
• 英文别名: di-n-butyl (methoxycarbonyl)phosphonate；Phosphinecarboxylic acid, dibutoxy-, methyl ester, oxide；methyl dibutoxyphosphorylformate
• CAS: 72304-81-5
• 化学式: C₁₀H₂₁O₅P
• 分子量: 252.247
• InChiKey: HEGJQRZSAFDZAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  di-n-butyl methoxycarbonylphosphonate 在 sodium hydroxide 作用下， 反应 1.0h， 生成 O-(正丁基)膦酸钠
  参考文献：
  名称：

  Synthesis of esters of phosphonoformic acid and their antiherpes activity

  摘要：

  Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.

  DOI：

  10.1021/jm00356a028
• 作为产物：
  描述：

  三丁基,三丁酯 、 氯甲酸甲酯 反应 6.0h， 生成 di-n-butyl methoxycarbonylphosphonate
  参考文献：
  名称：

  Phosphonoformic acid esters and pharmaceutical compositions containing

  摘要：

  一种药物制剂，其活性成分为式##STR1##中的化合物，其中R.sub.1和R.sub.2相同或不同，且每个都选自氢，含1-6个碳原子的烷基，含3-6个碳原子的环烷基，含4-6个碳原子的环烷基-烷基，1-金刚烷基，2-金刚烷基，苄基；以及式##STR2##中的苯基，其中R.sub.4和R.sub.5相同或不同，每个都选自氢，卤素，具有1、2或3个碳原子的烷基，具有1、2或3个碳原子的烷氧基，具有2-7个碳原子的烷氧羰基和具有2-7个碳原子的烷基羰基；或R.sub.4和R.sub.5在苯环中形成直链饱和烷基链，具有3或4个碳原子，与相邻位置即2,3-或3,4-相连；R.sub.3选自氢，含1-8个碳原子的烷基，含3-8个碳原子的环烷基，含4-8个碳原子的环烷基-烷基，1-金刚烷基，2-金刚烷基，苄基；以及式##STR3##中的苯基，其中R.sub.4和R.sub.5具有上述含义；但要求R.sub.1、R.sub.2和R.sub.3中至少有一个是如上定义的烷基，环烷基或环烷基-烷基，或1-金刚烷基，2-金刚烷基或苄基；并且当R.sub.3为H时，R.sub.1和R.sub.2中的一个是如上定义的烷基，环烷基或环烷基-烷基，或1-金刚烷基，2-金刚烷基或苄基，另一个是H；或其生理上可接受的盐或其光学异构体；式I内的新化合物，其制备方法以及它们的药用。

  公开号：

  US04591583A1

文献信息

• Aliphatic derivatives of phosphonoformic acid, pharmaceutical compositions and methods for combating virus infections
  申请人：Astra Läkemedel Aktiebolag

  公开号：EP0003007A2

  公开（公告）日：1979-07-11

  1. A pharmaceutical preparation containing as active ingredient a compound of the formula wherein R, and R2 are the same or different, and each is selected from the group consisting of hydrogen, alkyl groups containing 1-6 carbon atoms; cycloalkyl groups containing 3-6 carbon atoms; cycloalkyl-alkyl groups containing 4-6 carbon atoms: 1-adamantyl; 2-adamantyl, benzyl; and phenyl groups of the formula wherein R. and R5 are the same or different, and each is selected from the group consisting of hydrogen, halogen, alkyl having 1, 2, or 3 carbon atoms, alkoxy having 1, 2, or 3 carbon atoms, alkoxycarbonyl having 2-7 carbon atoms and alkylcarbonyl groups having 2-7 carbon atoms; or R. and R5 together form a straight saturated alkylene chain having 3 or 4 carbon atoms and being bound to adjacent positions, i.e. 2,3- or 3,4- in the phenyl ring; and R3 is selected from the group consisting of hydrogen, alkyl groups containing 1-8 carbon atoms; cycloalkyl groups containing 3-8 carbon atoms; cycloalkyl-alkyl groups containing 4-8 carbon atoms; 1-adamantyl; 2- adamantyl; benzyl; and phenyl groups of the formula wherein R4 and Rs have the meaning given above; provided that at least one of the groups R,, R2 and R3 is alkyl, cycloalkyl, or cycloalkyl-alkyl as defined above, or 1-adamantyl, 2-adamantyl, or benzyl; and provided that when R3 is H, then one of R, and R2 is alkyl, cycloalkyl, or cycloalkyl-alkyl as defined above, or 1-adamantyl, 2-adamantyl, or benzyl and the other of R, and R2 is H; or a physiologically acceptable salt or an optical isomer thereof; novel compounds within formula I, methods for their preparation and their medicinal use.

  1.一种药物制剂，其活性成分为如下式中的化合物 其中 R 和 R2 相同或不同，且各自选自由下列组成的组氢、含 1-6 个碳原子的烷基、含 3-6 个碳原子的环烷基、含 4-6 个碳原子的环烷基-烷基：1-金刚烷基；2-金刚烷基；苄基；以及式中的苯基。 其中 R.和 R5 相同或不同，且各自选自由氢、卤素、具有 1、2 或 3 个碳原子的烷基、具有 1、2 或 3 个碳原子的烷氧基、具有 2-7 个碳原子的烷氧羰基和具有 2-7 个碳原子的烷基羰基组成的组；或 R.和 R5 共同形成具有 3 或 4 个碳原子的直链饱和亚烷基，并结合到苯基环的相邻位置，即 2,3- 或 3,4- 位； R3 选自氢、含 1-8 个碳原子的烷基、含 3-8 个碳原子的环烷基、含 4-8 个碳原子的环烷基-烷基、1-金刚烷基、2-金刚烷基、苄基和式中的苯基所组成的组。 其中 R4 和 Rs 具有上述含义；条件是基团 R、R2 和 R3 中至少有一个是如上定义的烷基、环烷基或环烷基-烷基，或 1-金刚烷基、2-金刚烷基或苄基；且当 R3 为 H 时，则 R 和 R2 中的一个为如上定义的烷基、环烷基或环烷基-烷基，或 1-金刚烷基、2-金刚烷基或苄基，而 R 和 R2 中的另一个为 H；或其生理上可接受的盐或光学异构体；式 I 内的新型化合物、其制备方法及其药用用途。
• NOREN, J. O.;HELGSTRAND, E.;JOHANSSON, N. G.;MISIORNY, A.;STENING, G., J. MED. CHEM., 1983, 26, N 2, 264-270
  作者：NOREN, J. O.、HELGSTRAND, E.、JOHANSSON, N. G.、MISIORNY, A.、STENING, G.

  DOI：——

  日期：——
• US4386081A
  申请人：——

  公开号：US4386081A

  公开（公告）日：1983-05-31
• US4591583A
  申请人：——

  公开号：US4591583A

  公开（公告）日：1986-05-27
• Synthesis of esters of phosphonoformic acid and their antiherpes activity
  作者：Jan O. Noren、Erik Helgstrand、Nils G. Johansson、Alfons Misiorny、Goeran Stening

  DOI：10.1021/jm00356a028

  日期：1983.2

  Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.