N-[8-(diethylphosphono)octyl]phthalimide | 265323-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-[8-(diethylphosphono)octyl]phthalimide
• 英文别名: 2-(8-Diethoxyphosphoryloctyl)isoindole-1,3-dione
• CAS: 265323-08-8
• 化学式: C₂₀H₃₀NO₅P
• 分子量: 395.436
• InChiKey: GSCOSVCZSDIGDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[8-(diethylphosphono)octyl]phthalimide 在 盐酸 、 sodium ethanolate 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 38.0h， 生成 6-amino-1-[8-(diethylphosphono)octyl]uracil
  参考文献：
  名称：

  Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of Escherichia coli Thymidine Phosphorylase

  摘要：

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.

  DOI：

  10.1021/jm9911377
• 作为产物：
  描述：

  N-(8-溴辛基)邻苯二甲酰亚胺 、 亚磷酸三乙酯 反应 12.0h， 以96%的产率得到N-[8-(diethylphosphono)octyl]phthalimide
  参考文献：
  名称：

  Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of Escherichia coli Thymidine Phosphorylase

  摘要：

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.

  DOI：

  10.1021/jm9911377

文献信息

• Cameron, David G.; Hudson, Harry R.; Pianka, Max, Phosphorus, Sulfur and Silicon and the Related Elements, 1993, vol. 83, # 1-4, p. 21 - 38
  作者：Cameron, David G.、Hudson, Harry R.、Pianka, Max

  DOI：——

  日期：——
• Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of <i>Escherichia </i><i>coli</i> Thymidine Phosphorylase
  作者：Antonio Esteban-Gamboa、Jan Balzarini、Robert Esnouf、Erik De Clercq、María-José Camarasa、María-Jesús Pérez-Pérez

  DOI：10.1021/jm9911377

  日期：2000.3.1

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.