10-(prop-2-ynyloxy)camptothecin | 948830-82-8

• 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: 10-(prop-2-ynyloxy)camptothecin
• 英文别名: (19S)-19-ethyl-19-hydroxy-7-prop-2-ynoxy-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)-heptaene-14,18-dione
• CAS: 948830-82-8
• 化学式: C₂₃H₁₈N₂O₅
• 分子量: 402.406
• InChiKey: JXUAMIBZOFMFBJ-QHCPKHFHSA-N

物化性质

• 沸点：
  798.6±60.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10-(prop-2-ynyloxy)camptothecin 在 copper(l) iodide 、 茴香硫醚 、 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 26.0h， 生成 6-[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-hydroxyhexanamide
  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
• 作为产物：
  描述：

  10-羟基喜树碱 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以87 %的产率得到10-(prop-2-ynyloxy)camptothecin
  参考文献：
  名称：

  10-alkoxy-5-spiro CPT的设计、合成及体外初步生物学评价

  摘要：

  以简便的方法合成了一系列10-烷氧基-5-螺环喜树碱衍生物。一方面，这些化合物的溶解度明显改变；另一方面，这些5-螺环喜树碱衍生物中的大多数对MGC803细胞系表现出更好的抑制活性。

  DOI：

  10.1016/j.tet.2023.133325

文献信息

• 人工合成钯纳米酶催化含有酚羟基连接的化合物的应用
  申请人：南开大学

  公开号：CN113336631B

  公开（公告）日：2022-12-02

  本发明提供了人工钯纳米酶催化催化含有酚羟基连接的化合物的应用，钯纳米酶催化含有至少一个苯环的芳香官能团连接的炔丙氧基碳氧键断裂，含有至少一个苯环的芳香官能团包括但不限于荧光素、苯环、吡啶环、联苯、萘、蒽、香豆素或喜树碱，含有至少一个苯环的芳香官能团可以连接氧或氧‑羰基氧或氧‑羰基氧‑氧，本发明通过构建不同的人工钯纳米酶，并可以实现多种分子的碳氧键的断裂，应用在细胞成像中和癌症治疗中。
• 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.
• Design, synthesis of 10-alkoxy-5-spiro CPT and preliminary biological evaluation in vitro
  作者：Xi Ke、Xianheng Wang、Yuan Liu、Yuhe Wang、Changkuo Zhao

  DOI：10.1016/j.tet.2023.133325

  日期：2023.4

  A series of 10-alkoxy-5-spirocycle campthothecin derivatives were synthesized in a convenient method. On the one hand, the solubility of these compounds was obviously modified; on the other hand, most of these 5-spirocycle campthothecin derivatives showed a better inhibition activity against MGC803 cell line.

  以简便的方法合成了一系列10-烷氧基-5-螺环喜树碱衍生物。一方面，这些化合物的溶解度明显改变；另一方面，这些5-螺环喜树碱衍生物中的大多数对MGC803细胞系表现出更好的抑制活性。