diethyl chloromethylphosphonate | 158421-59-1

• 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 chloromethylphosphonate
• 英文别名: diethylphosphonoacetyl chloride；(diethylphosphono)formic chloride；Diethyl (chlorocarbonyl)phosphonate；diethoxyphosphorylformyl chloride
• CAS: 158421-59-1
• 化学式: C₅H₁₀ClO₄P
• 分子量: 200.559
• InChiKey: UVASJLPRXBXQMW-UHFFFAOYSA-N

物化性质

• 沸点：
  224.6±23.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  齐多夫定 、 diethyl chloromethylphosphonate 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 以80%的产率得到3'-azido-3'-deoxy-5'-O-[(diethoxyphosphono)carbonyl]thymidine
  参考文献：
  名称：

  Antiviral compounds and methods of administration

  摘要：

  这项发明提供了表现出卓越抗病毒活性的亲脂性膦酸/核苷酸共轭物，包括对耐药HIV菌株的活性。该发明的化合物包括膦酸/核苷酸共轭物，其中膦酸的羧基和磷酰基被酯化，使化合物含有至少一个亲脂性基团和至少一个核苷酸基团。

  公开号：

  US06686462B2
• 作为产物：
  描述：

  三光气 、 亚磷酸三乙酯 在 N,N-二甲基甲酰胺 作用下， 以65%的产率得到diethyl chloromethylphosphonate
  参考文献：
  名称：

  Inhibition of Human Immunodeficiency Virus Type 1 Replication by Phosphonoformate- and Phosphonoacetate-2',3'-Dideoxy-3'-thiacytidine Conjugates

  摘要：

  The synthesis of potential ''combined prodrugs'' where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N-4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 Of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 mu M, while IC50 for BCH-189 in this system was 0.1 mu M. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t(1/2) values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti-HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.

  DOI：

  10.1021/jm00040a014

文献信息

• Synthesis and reactivity of diethyl phosphonomethyltriflate
  作者：Dennis P. Phillion、Steven S. Andrew

  DOI：10.1016/s0040-4039(00)84289-6

  日期：1986.1
• Chen, Ya Ping; Chantegrel, Bernard; Deshayes, Christian, Heterocycles, 1995, vol. 41, # 1, p. 175 - 186
  作者：Chen, Ya Ping、Chantegrel, Bernard、Deshayes, Christian

  DOI：——

  日期：——
• US6686462B2
  申请人：——

  公开号：US6686462B2

  公开（公告）日：2004-02-03
• [EN] ANTIVIRAL PHOSPHONATE PRODRUGS OF NUCLEOSIDES AND NUCLEOSIDE ANALOGUES<br/>[FR] PROMEDICAMENTS AU PHOSPHONATE ANTIVIRAUX DE NUCLEOSIDES ET D'ANALOGUES DE NUCLEOSIDES
  申请人：DANA-FARBER CANCER INSTITUTE

  公开号：WO1998038202A1

  公开（公告）日：1998-09-03

  (EN) The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.(FR) Cette invention se rapporte à des conjugués de nucléosides et d'acide phosphonique lipophile, qui possèdent une action antivirale exceptionnelle, notamment une action contre les souches de VIH résistantes aux médicaments. Les composés de cette invention sont notamment des conjugués de nucléosides et d'acide phosphonique, dans lesquels le groupe carboxyle et les groupes phosphonyles de l'acide phosphonique sont esterifiés pour que le composé obtenu contiennent au moins un groupe lipophile et au moins groupe nucléoside.
• Antiviral compounds and methods of administration
  申请人：The Regents of the University of California

  公开号：US06686462B2

  公开（公告）日：2004-02-03

  The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.

  这项发明提供了表现出卓越抗病毒活性的亲脂性膦酸/核苷酸共轭物，包括对耐药HIV菌株的活性。该发明的化合物包括膦酸/核苷酸共轭物，其中膦酸的羧基和磷酰基被酯化，使化合物含有至少一个亲脂性基团和至少一个核苷酸基团。