methyl (chloro(4-chlorophenoxy)phosphoryl)-D-alaninate | 1185924-11-1

• 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: methyl (chloro(4-chlorophenoxy)phosphoryl)-D-alaninate
• CAS: 1185924-11-1
• 化学式: C₁₀H₁₂Cl₂NO₄P
• 分子量: 312.089
• InChiKey: KGLVSCYDEKUYIH-XNQUEAFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  18.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (chloro(4-chlorophenoxy)phosphoryl)-D-alaninate 、 2'-C-甲基胞嘧啶核苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 生成 5'-O-[(4-chlorophenoxy)[[(1R)-2-methoxy-1-methyl-2-oxoethyl]amino]phosphinyl]-2'-C-methylcytidine
  参考文献：
  名称：

  Phosphoramidate Prodrugs of 2′-C-Methylcytidine for Therapy of Hepatitis C Virus Infection

  摘要：

  The application of a phosphoramidate prodrug approach to 2'-C-methylcytidine (NM107), the first nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, is reported. 2'-C-Methylcytidine, as its valyl ester prodrug (NM283), was efficacious in reducing the viral load in patients infected with HCV. Several of the phosphoramidates prepared demonstrated a 10- to 200-fold superior potency with respect to the parent nucleoside in the cell-based replicon assay. This is due to higher levels of 2'-C-methylcytidine triphosphate in the cells. These prodrugs are efficiently activated and converted to the triphosphate in hepatocytes of several species. Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides.

  DOI：

  10.1021/jm900447q

文献信息

• Aryl phosphate derivatives of d4T having anti-HIV activity
  申请人：Parker Hughes Institute

  公开号：US06350736B1

  公开（公告）日：2002-02-26

  Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.

  d4T的芳基磷酸酯衍生物，在芳基上对位溴取代，显示出明显增强的抗HIV活性，而无不良水平的细胞毒活性。特别是，这些衍生物是HIV反转录酶的强效抑制剂。在本发明的首选方面，芳基磷酸酯基的磷进一步取代为氨基酸残基，该残基可以酯化或取代，如甲氧基丙氨基基团。