p-pentylphenyl methoxyalaninyl phosphorochloridate | 147907-37-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: p-pentylphenyl methoxyalaninyl phosphorochloridate
• 英文别名: methyl (2S)-2-[[chloro-(4-pentylphenoxy)phosphoryl]amino]propanoate
• CAS: 147907-37-7
• 化学式: C₁₅H₂₃ClNO₄P
• 分子量: 347.779
• InChiKey: GDBSXYQZKMWJCS-BJDAYTSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  齐多夫定 、 p-pentylphenyl methoxyalaninyl phosphorochloridate 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 以57%的产率得到3'-azidothymidine 5'-
  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
• 作为产物：
  描述：

  4-戊基苯酚 在 三乙胺 、 三氯氧磷 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 p-pentylphenyl methoxyalaninyl phosphorochloridate
  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

• 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.