20-Ethyl-20-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.9.0.02,11.04,9.015,21]docosa-1(22),2,4,6,8,10,15(21)-heptaene-10-carbaldehyde | 902781-58-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 20-Ethyl-20-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.9.0.02,11.04,9.015,21]docosa-1(22),2,4,6,8,10,15(21)-heptaene-10-carbaldehyde
• CAS: 902781-58-2
• 化学式: C₂₂H₁₈N₂O₅
• 分子量: 390.395
• InChiKey: TZVGQMPCPAHRBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  20-Ethyl-20-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.9.0.02,11.04,9.015,21]docosa-1(22),2,4,6,8,10,15(21)-heptaene-10-carbaldehyde 、 3,4-二氯苯胺 在 ytterbium(III) triflate 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以24.8%的产率得到
  参考文献：
  名称：

  New homocamptothecins: Synthesis, antitumor activity, and molecular modeling

  摘要：

  Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 91, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.046
• 作为产物：
  描述：

  7-Hydroxymethylhomocamptothecin 在 selenium(IV) oxide 作用下， 生成 20-Ethyl-20-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.9.0.02,11.04,9.015,21]docosa-1(22),2,4,6,8,10,15(21)-heptaene-10-carbaldehyde
  参考文献：
  名称：

  作为有效拓扑异构酶 I 抑制剂的 7-烯基高喜树碱的合成和生物学评价

  摘要：

  Homocamptothecin (hCPT) 是一种喜树碱 (CPT) 衍生物，具有七元 β-羟基内酯 E 环，具有更高的内酯稳定性并提高拓扑异构酶 I (Topo I) 抑制活性。为了提高高喜树碱的抗肿瘤活性，基于以CPT为原料的半合成路线，设计并合成了一系列7-烯基-高喜树碱衍生物。大多数合成的化合物对 A-549 肿瘤细胞系的细胞毒活性高于拓扑替康 (TPT)。一些化合物如 2a 和 2o 显示出广泛的体外抗肿瘤谱，并表现出优异的 Topo I 抑制活性。

  DOI：

  10.1002/cbdv.201100195

文献信息

• New homocamptothecins: Synthesis, antitumor activity, and molecular modeling
  作者：Zhenyuan Miao、Chunquan Sheng、Wannian Zhang、Haitao Ji、Jing Zhang、Lücheng Shao、Liang You、Min Zhang、Jianzhong Yao、Xiaoyin Che

  DOI：10.1016/j.bmc.2007.10.046

  日期：2008.2.1

  Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 91, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of 7-Alkenyl Homocamptothecins as Potent Topoisomerase I Inhibitors
  作者：Lingjian Zhu、Xianghua Zhang、Ning Lei、Wenfeng Liu、Zhenyuan Miao、Chunlin Zhuang、Chunquan Sheng、Wei Guo、Guoqiang Dong、Jianzhong Yao、Pengfei Cheng、Wannian Zhang

  DOI：10.1002/cbdv.201100195

  日期：2012.6

  Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven‐membered β‐hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7‐alkenyl‐homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT

  Homocamptothecin (hCPT) 是一种喜树碱 (CPT) 衍生物，具有七元 β-羟基内酯 E 环，具有更高的内酯稳定性并提高拓扑异构酶 I (Topo I) 抑制活性。为了提高高喜树碱的抗肿瘤活性，基于以CPT为原料的半合成路线，设计并合成了一系列7-烯基-高喜树碱衍生物。大多数合成的化合物对 A-549 肿瘤细胞系的细胞毒活性高于拓扑替康 (TPT)。一些化合物如 2a 和 2o 显示出广泛的体外抗肿瘤谱，并表现出优异的 Topo I 抑制活性。