Ethyl 3-(3-bromo-4-methoxyphenyl)-3-hydroxypropanoate | 1457750-52-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Ethyl 3-(3-bromo-4-methoxyphenyl)-3-hydroxypropanoate
• CAS: 1457750-52-5
• 化学式: C₁₂H₁₅BrO₄
• 分子量: 303.153
• InChiKey: IWNJMGFCENFWJD-UHFFFAOYSA-N

物化性质

• 沸点：
  403.1±45.0 °C(Predicted)
• 密度：
  1.418±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 3-(3-bromo-4-methoxyphenyl)-3-hydroxypropanoate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 1-(3-溴-4-甲氧基苯基)-1,3-丙二醇
  参考文献：
  名称：

  Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B

  摘要：

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.

  DOI：

  10.1021/jm7012216
• 作为产物：
  描述：

  3-溴-4-甲氧基苯甲醛 、 乙酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 Ethyl 3-(3-bromo-4-methoxyphenyl)-3-hydroxypropanoate
  参考文献：
  名称：

  Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B

  摘要：

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.

  DOI：

  10.1021/jm7012216

文献信息

• Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B
  作者：K. Raja Reddy、Michael C. Matelich、Bheemarao G. Ugarkar、Jorge E. Gómez-Galeno、Jay DaRe、Kristin Ollis、Zhili Sun、William Craigo、Timothy J. Colby、James M. Fujitaki、Serge H. Boyer、Paul D. van Poelje、Mark D. Erion

  DOI：10.1021/jm7012216

  日期：2008.2.1

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.