(S)-(1-(14-azido-2-oxo-6,9,12-trioxa-3-azatetradecyl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl (4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl) ethane-1,2-diylbis(methylcarbamate) | 1219705-85-7

• 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)-(1-(14-azido-2-oxo-6,9,12-trioxa-3-azatetradecyl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl (4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl) ethane-1,2-diylbis(methylcarbamate)
• 英文别名: [(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] N-[2-[[1-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethylamino]-2-oxoethyl]-5-methoxy-2-methyl-4,7-dioxoindol-3-yl]methoxycarbonyl-methylamino]ethyl]-N-methylcarbamate
• CAS: 1219705-85-7
• 化学式: C₄₉H₅₇N₉O₁₅
• 分子量: 1012.04
• InChiKey: KCBLLKSKZUNNNH-GGCSAXROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  73
• 可旋转键数：
  25
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  258
• 氢给体数：
  2
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  C₃₅H₅₀N₁₀O₁₀ 、 (S)-(1-(14-azido-2-oxo-6,9,12-trioxa-3-azatetradecyl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl (4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl) ethane-1,2-diylbis(methylcarbamate) 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 以48%的产率得到C₈₄H₁₀₇N₁₉O₂₅
  参考文献：
  名称：

  The Synthesis of a c(RGDyK) Targeted SN38 Prodrug with an Indolequinone Structure for Bioreductive Drug Release

  摘要：

  Preparation of a novel c(RGDyK) targeted SN38 prodrug Incorporating an indolequinone structure for bioreductively triggered drug release is described. This design yields a prodrug that targets surface molecules on tumor cells (alpha(v)beta(3) integrins) and releases drug under bioreductive conditions. There are three moieties in the prodrug design, namely a therapeutic drug SN38, an indolequinone structure serving as a drug releasing trigger, and an alpha(v)beta(3) integrin targeting peptide c(RGDyK). Preliminary studies showed that SN38 is released In the presence of a bioreductive enzyme (DT-diaphorase).

  DOI：

  10.1021/ol1002626
• 作为产物：
  描述：

  (1-(14-azido-2-oxo-6,9,12-trioxa-3-azatetradecyl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl (2-((chlorocarbonyl)(methyl)amino)ethyl)(methyl)carbamate 、 7-乙基-10-羟基喜树碱 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以60.1 mg的产率得到(S)-(1-(14-azido-2-oxo-6,9,12-trioxa-3-azatetradecyl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl (4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl) ethane-1,2-diylbis(methylcarbamate)
  参考文献：
  名称：

  The Synthesis of a c(RGDyK) Targeted SN38 Prodrug with an Indolequinone Structure for Bioreductive Drug Release

  摘要：

  Preparation of a novel c(RGDyK) targeted SN38 prodrug Incorporating an indolequinone structure for bioreductively triggered drug release is described. This design yields a prodrug that targets surface molecules on tumor cells (alpha(v)beta(3) integrins) and releases drug under bioreductive conditions. There are three moieties in the prodrug design, namely a therapeutic drug SN38, an indolequinone structure serving as a drug releasing trigger, and an alpha(v)beta(3) integrin targeting peptide c(RGDyK). Preliminary studies showed that SN38 is released In the presence of a bioreductive enzyme (DT-diaphorase).

  DOI：

  10.1021/ol1002626

文献信息

• The Synthesis of a c(RGDyK) Targeted SN38 Prodrug with an Indolequinone Structure for Bioreductive Drug Release
  作者：Baohua Huang、Ankur Desai、Shengzhuang Tang、Thommey P. Thomas、James R. Baker

  DOI：10.1021/ol1002626

  日期：2010.4.2

  Preparation of a novel c(RGDyK) targeted SN38 prodrug Incorporating an indolequinone structure for bioreductively triggered drug release is described. This design yields a prodrug that targets surface molecules on tumor cells (alpha(v)beta(3) integrins) and releases drug under bioreductive conditions. There are three moieties in the prodrug design, namely a therapeutic drug SN38, an indolequinone structure serving as a drug releasing trigger, and an alpha(v)beta(3) integrin targeting peptide c(RGDyK). Preliminary studies showed that SN38 is released In the presence of a bioreductive enzyme (DT-diaphorase).