(S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 4,4-bis(diethoxyphosphoryl)butanoate | 1008144-92-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 4,4-bis(diethoxyphosphoryl)butanoate
• CAS: 1008144-92-0
• 化学式: C₃₂H₄₀N₂O₁₁P₂
• 分子量: 690.624
• InChiKey: WGLARVHROJBBPV-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.27
• 重原子数：
  47.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  158.55
• 氢给体数：
  0.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 4,4-bis(diethoxyphosphoryl)butanoate 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以94%的产率得到Camdronate
  参考文献：
  名称：

  Chemotherapeutic bone-targeted bisphosphonate prodrugs with hydrolytic mode of activation

  摘要：

  Osseous tissues are considered to be limited as therapeutic target sites due to their biological properties. We have designed and synthesized two kinds of hydrolytically activated chemotherapeutic prodrugs containing bisphosphonate, a bone-targeting moiety. The first can be conjugated to drug molecules with an available hydroxy group; the drug is attached to the bisphosphonate component through an ester-labile linkage. The second is for use with drug molecules with amine functional group. In this case, a self-immolative linker is used to attach the drug to the bisphosphonate component through a carbonate-labile linkage. The concept was demonstrated using the drugs camptothecin, which has a hydroxy functional group, and tryptophan, which is a model molecule for a drug with amine functionality. Both prodrugs showed significant binding capability to hydroxyapatite, the major component of bone, and were hydrolytically activated under physiological conditions. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.029
• 作为产物：
  描述：

  喜树碱 、 4,4-bis(diethylphosphono)butanoic acid chloride 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以447.1 mg的产率得到(S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 4,4-bis(diethoxyphosphoryl)butanoate
  参考文献：
  名称：

  Chemotherapeutic bone-targeted bisphosphonate prodrugs with hydrolytic mode of activation

  摘要：

  Osseous tissues are considered to be limited as therapeutic target sites due to their biological properties. We have designed and synthesized two kinds of hydrolytically activated chemotherapeutic prodrugs containing bisphosphonate, a bone-targeting moiety. The first can be conjugated to drug molecules with an available hydroxy group; the drug is attached to the bisphosphonate component through an ester-labile linkage. The second is for use with drug molecules with amine functional group. In this case, a self-immolative linker is used to attach the drug to the bisphosphonate component through a carbonate-labile linkage. The concept was demonstrated using the drugs camptothecin, which has a hydroxy functional group, and tryptophan, which is a model molecule for a drug with amine functionality. Both prodrugs showed significant binding capability to hydroxyapatite, the major component of bone, and were hydrolytically activated under physiological conditions. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.029