4-propylphenyl dichlorophosphate | 916893-01-1

• 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: 4-propylphenyl dichlorophosphate
• 英文别名: 1-Dichlorophosphoryloxy-4-propylbenzene；1-dichlorophosphoryloxy-4-propylbenzene
• CAS: 916893-01-1
• 化学式: C₉H₁₁Cl₂O₂P
• 分子量: 253.065
• InChiKey: SICMCRXUYHOXBB-UHFFFAOYSA-N

物化性质

• 沸点：
  296.6±19.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-propylphenyl dichlorophosphate 在 N-甲基咪唑 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (S)-2-[[(2R,4R)-4-(5-Methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-[1,3]dioxolan-2-ylmethoxy]-(4-propyl-phenoxy)-phosphorylamino]-propionic acid methyl ester
  参考文献：
  名称：

  Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies

  摘要：

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.008
• 作为产物：
  描述：

  4-丙基苯酚 在 三乙胺 、 三氯氧磷 作用下， 以 乙醚 为溶剂， 生成 4-propylphenyl dichlorophosphate
  参考文献：
  名称：

  Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT

  摘要：

  Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity iri TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies.

  DOI：

  10.1021/jm00060a013

文献信息

• METHOD FOR PRODUCING AN AMINO GROUP-CONTAINING PHOSPHATE COMPOUND, AND A FLAME-RETARDANT RESIN AND FLAME-RETARDANT RESIN COMPOSITION
  申请人：Kamata Hirotoshi

  公开号：US20100298506A1

  公开（公告）日：2010-11-25

  The present invention relates to a method for producing an amino group-containing phosphate compound, by which the compound can be easily synthesized through a one-step reaction. The method for producing an amino group-containing phosphate compound comprises reacting an aminophenol compound represented by the general formula (1) with a dichlorophosphoric acid compound represented by the general formula (2): (where X 1 , X 2 , X 3 , X 4 and X 5 each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms) in the presence of an inorganic basic compound in an aprotic organic solvent, to obtain a amino group-containing phosphate compound represented by the following general formula (3) where X 1 , X 2 , X 3 , X 4 and X 5 are defined in the same way as in the general formula (2).

  本发明涉及一种制备含氨基磷酸盐化合物的方法，通过该方法，该化合物可以通过一步反应轻松合成。制备含氨基磷酸盐化合物的方法包括在无水有机溶剂中，在无机碱的存在下，将由通式（1）表示的氨基酚化合物与由通式（2）表示的二氯磷酸化合物反应（其中X1、X2、X3、X4和X5分别表示氢原子或具有1至3个碳原子的烷基），以得到由以下通式（3）表示的含氨基磷酸盐化合物（其中X1、X2、X3、X4和X5的定义与通式（2）中相同）。
• PROCESS FOR PRODUCTION OF AMINATED PHOSPHORIC ACID ESTER COMPOUND, FLAME-RETARDANT RESIN, AND FLAME-RETARDANT RESIN COMPOSITION
  申请人：SHOWA HIGHPOLYMER CO., LTD.

  公开号：EP2036911A1

  公开（公告）日：2009-03-18

  The present invention relates to a method for producing an amino group-containing phosphate compound, by which the compound can be easily synthesized through a one-step reaction. The method for producing an amino group-containing phosphate compound comprises reacting an aminophenol compound represented by the general formula (1) with a dichlorophosphoric acid compound represented by the general formula (2): (where X1, X2, X3, X4 and X5 each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms) in the presence of an inorganic basic compound in an aprotic organic solvent, to obtain a amino group-containing phosphate compound represented by the following general formula (3) where X1, X2, X3, X4 and X5 are defined in the same way as in the general formula (2).

  本发明涉及一种生产含氨基的磷酸酯化合物的方法，通过该方法，可通过一步反应轻松合成该化合物。生产含氨基的磷酸酯化合物的方法包括使通式（1）代表的氨基苯酚化合物反应 与通式（2）所代表的二氯磷酸化合物反应： (其中 X1、X2、X3、X4 和 X5 各代表一个氢原子或一个具有 1 至 3 个碳原子的烷基），在无机碱性化合物存在下，在非烷基有机溶剂中反应，得到由以下通式 (3) 代表的含氨基的磷酸化合物 其中 X1、X2、X3、X4 和 X5 的定义与通式（2）相同。
• Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies
  作者：Yuzeng Liang、Janarthanan Narayanasamy、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1016/j.bmc.2005.11.008

  日期：2006.4

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.
• Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT
  作者：Christopher McGuigan、Ranjith N. Pathirana、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm00060a013

  日期：1993.4

  Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity iri TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies.