(dimethylphosphono)formic chloride | 98025-47-9

• 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: (dimethylphosphono)formic chloride
• 英文别名: chlorocarbonyl-phosphonic acid dimethyl ester；Chlorcarbonyl-phosphonsaeure-dimethylester；Dimethoxyphosphorylformyl chloride
• CAS: 98025-47-9
• 化学式: C₃H₆ClO₄P
• 分子量: 172.505
• InChiKey: WSDHNMFMPVONCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  (dimethylphosphono)formic chloride 、 拉米夫定 在 吡啶 作用下， 反应 3.0h， 以14%的产率得到cis-2-<<<(dimethylphosphono)carbonyl>oxy>methyl>-5-4-<(dimethylphosphono)formyl>cytosin-1'-yl>-1,3-oxathiolane
  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
• 作为产物：
  描述：

  (dimethylphosphono)formic acid 在 氯化亚砜 作用下， 以46%的产率得到(dimethylphosphono)formic chloride
  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

• Inhibition of Human Immunodeficiency Virus Type 1 Replication by Phosphonoformate- and Phosphonoacetate-2',3'-Dideoxy-3'-thiacytidine Conjugates
  作者：Anne-Sophie Charvet、Michel Camplo、Philippe Faury、Jean-Christophe Graciet、Nicolas Mourier、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1021/jm00040a014

  日期：1994.7

  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.