fumaric acid; methyl (2S)-2-[(2R)-2-[2-(6-aminopurin-9-yl)ethoxymethyl]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-3-yl]propanoate | 1200115-70-3

• 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: fumaric acid; methyl (2S)-2-[(2R)-2-[2-(6-aminopurin-9-yl)ethoxymethyl]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-3-yl]propanoate
• 英文别名: (E)-but-2-enedioic acid;methyl (2S)-2-[(2R)-2-[2-(6-aminopurin-9-yl)ethoxymethyl]-2-oxo-1,3,2λ5-oxazaphosphinan-3-yl]propanoate
• CAS: 1200115-70-3
• 化学式: C₄H₄O₄*C₁₅H₂₃N₆O₅P
• 分子量: 514.432
• InChiKey: WXMGXJANYOFMTF-YWRAOZIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.57
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  209
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  methyl (2S)-2-[(2R)-2-[2-(6-aminopurin-9-yl)ethoxymethyl]-2-oxo-1,3,2lambda5-oxazaphosphinan-3-yl]propanoate 、 富马酸 以 乙腈 为溶剂， 反应 2.0h， 生成 fumaric acid; methyl (2S)-2-[(2R)-2-[2-(6-aminopurin-9-yl)ethoxymethyl]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-3-yl]propanoate
  参考文献：
  名称：

  Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors

  摘要：

  A series of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) were synthesized and their anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells, with adefovir dipivoxil as a reference drug. In the cell assays, compounds 7b and 7d exhibited anti-HBV activity comparable to that of adefovir dipivoxil, while compound 7c, with an IC50 value of 0.12 mu M, was found to be three times more potent than the reference compound. In vitro stability studies showed that (S-P,S)-7c, the diastereomer of compound 7c, was stable in human blood plasma but underwent rapid metabolism to release the parent drug PMEA in liver microsomes. The possible metabolic pathway of (S-P,S)-7c in human liver microsomes was described. These findings suggest that compound (S-P,S)-7c is a promising anti-HBV drug candidate for further development. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.072

文献信息

• Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors
  作者：Peng Lu、Jiangxia Liu、Yuya Wang、Xiaoyan Chen、Yushe Yang、Ruyun Ji

  DOI：10.1016/j.bmcl.2009.10.072

  日期：2009.12

  A series of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) were synthesized and their anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells, with adefovir dipivoxil as a reference drug. In the cell assays, compounds 7b and 7d exhibited anti-HBV activity comparable to that of adefovir dipivoxil, while compound 7c, with an IC50 value of 0.12 mu M, was found to be three times more potent than the reference compound. In vitro stability studies showed that (S-P,S)-7c, the diastereomer of compound 7c, was stable in human blood plasma but underwent rapid metabolism to release the parent drug PMEA in liver microsomes. The possible metabolic pathway of (S-P,S)-7c in human liver microsomes was described. These findings suggest that compound (S-P,S)-7c is a promising anti-HBV drug candidate for further development. (C) 2009 Elsevier Ltd. All rights reserved.