20-Ethyl-20-hydroxy-6,8-dimethyl-10-(pyridin-1-ium-1-ylmethyl)-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-14,18-dione;chloride | 1018960-77-4

• 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-6,8-dimethyl-10-(pyridin-1-ium-1-ylmethyl)-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-14,18-dione;chloride
• CAS: 1018960-77-4
• 化学式: C₂₉H₂₈N₃O₄*Cl
• 分子量: 518.012
• InChiKey: UPMYYGDLORFEEN-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.43
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  吡啶 、 12-(chloromethyl)-5-ethyl-5-hydroxy-9,11-dimethyl-1,4,5,13-tetrahydro-3H,15H-oxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione 以 二甲基亚砜 为溶剂， 以43.5%的产率得到20-Ethyl-20-hydroxy-6,8-dimethyl-10-(pyridin-1-ium-1-ylmethyl)-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-14,18-dione;chloride
  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

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.