5-[4-[[(19S)-19-ethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl]oxymethyl]triazol-1-yl]-N-hydroxypentanamide | 1436410-94-4

• 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: 5-[4-[[(19S)-19-ethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl]oxymethyl]triazol-1-yl]-N-hydroxypentanamide
• CAS: 1436410-94-4
• 化学式: C₂₈H₂₈N₆O₇
• 分子量: 560.566
• InChiKey: CBEWPDGJGLHJCA-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  169
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  10-羟基喜树碱 在 copper(l) iodide 、 茴香硫醚 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 50.0h， 生成 5-[4-[[(19S)-19-ethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl]oxymethyl]triazol-1-yl]-N-hydroxypentanamide
  参考文献：
  名称：

  Dual-acting histone deacetylase-topoisomerase I inhibitors

  摘要：

  Current chemotherapy regimens are comprised mostly of single-target drugs which are often plagued by toxic side effects and resistance development. A pharmacological strategy for circumventing these drawbacks could involve designing multivalent ligands that can modulate multiple targets while avoiding the toxicity of a single-targeted agent. Two attractive targets, histone deacetylase (HDAC) and topoisomerase I (Topo I), are cellular modulators that can broadly arrest cancer proliferation through a range of downstream effects. Both are clinically validated targets with multiple inhibitors in therapeutic use. We describe herein the design and synthesis of dual-acting histone deacetylase-topoisomerase I inhibitors. We also show that these dual-acting agents retain activity against HDAC and Topo I, and potently arrest cancer proliferation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.03.108

文献信息

• Dual-acting histone deacetylase-topoisomerase I inhibitors
  作者：William Guerrant、Vishal Patil、Joshua C. Canzoneri、Li-Pan Yao、Rebecca Hood、Adegboyega K. Oyelere

  DOI：10.1016/j.bmcl.2013.03.108

  日期：2013.6

  Current chemotherapy regimens are comprised mostly of single-target drugs which are often plagued by toxic side effects and resistance development. A pharmacological strategy for circumventing these drawbacks could involve designing multivalent ligands that can modulate multiple targets while avoiding the toxicity of a single-targeted agent. Two attractive targets, histone deacetylase (HDAC) and topoisomerase I (Topo I), are cellular modulators that can broadly arrest cancer proliferation through a range of downstream effects. Both are clinically validated targets with multiple inhibitors in therapeutic use. We describe herein the design and synthesis of dual-acting histone deacetylase-topoisomerase I inhibitors. We also show that these dual-acting agents retain activity against HDAC and Topo I, and potently arrest cancer proliferation. Published by Elsevier Ltd.