1,1-(ethylenedioxy)-8-ethyl-7,8-dihydroxy-1,2,3,5,7,8-hexahydro-6-oxa-3a-azacyclopenta[b]naphthalen-4-one | 929003-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: 1,1-(ethylenedioxy)-8-ethyl-7,8-dihydroxy-1,2,3,5,7,8-hexahydro-6-oxa-3a-azacyclopenta[b]naphthalen-4-one
• 英文别名: 4-ethyl-3,4-dihydroxyspiro[1,3,7,8-tetrahydropyrano[3,4-f]indolizine-6,2'-1,3-dioxolane]-10-one
• CAS: 929003-01-0
• 化学式: C₁₅H₁₉NO₆
• 分子量: 309.319
• InChiKey: KEFGMPREHXTEBR-UHFFFAOYSA-N

物化性质

• 沸点：
  624.1±55.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  90.15
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1,1-(ethylenedioxy)-8-ethyl-7,8-dihydroxy-1,2,3,5,7,8-hexahydro-6-oxa-3a-azacyclopenta[b]naphthalen-4-one 在 sodium periodate 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 0.5h， 以93.1%的产率得到formic acid 1,1-(ethylenedioxy)-5-oxo-7-propionyl-1,2,3,5-tetrahydroindolizin-6-ylmethyl ester
  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：

  4'-乙基-7'，8'-二氢-4'-羟基-螺[1,3-二氧戊环-2,6'（3'H）-[1H]吡喃并[3,4-f]吲哚嗪]-3′，10′（4′H）-二酮-d5 在 钾硼氢 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以79.5%的产率得到1,1-(ethylenedioxy)-8-ethyl-7,8-dihydroxy-1,2,3,5,7,8-hexahydro-6-oxa-3a-azacyclopenta[b]naphthalen-4-one
  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

• Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities
  作者：Zhenyuan Miao、Jing Zhang、Liang You、Juan Wang、Chunquan Sheng、Jiangzhong Yao、Wannian Zhang、Hao Feng、Wei Guo、Lei Zhou、Wenfeng Liu、Linjian Zhu、Pengfei Cheng、Xiaoying Che、Wenya Wang、Chuan Luo、Yulan Xu、Guoqiang Dong

  DOI：10.1016/j.bmc.2010.03.039

  日期：2010.5

  Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0. (c) 2010 Elsevier Ltd. All rights reserved.