3,8-Bis(ethoxycarbonylamino)-5-(5-ethoxycarbonylpentyl)-6-phenylphenanthridinium trifluoromethanesulfonate

• 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: 3,8-Bis(ethoxycarbonylamino)-5-(5-ethoxycarbonylpentyl)-6-phenylphenanthridinium trifluoromethanesulfonate
• 英文别名: Ethyl 6-[3,8-bis(ethoxycarbonylamino)-6-phenylphenanthridin-5-ium-5-yl]hexanoate;trifluoromethanesulfonate
• 化学式: CF₃O₃S*C₃₃H₃₈N₃O₆
• 分子量: 721.752
• InChiKey: OWDFYDZUCALVDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.26
• 重原子数：
  50
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  172
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3,8-Bis(ethoxycarbonylamino)-5-(5-ethoxycarbonylpentyl)-6-phenylphenanthridinium trifluoromethanesulfonate 在 氢溴酸 作用下， 反应 3.0h， 以87%的产率得到3,8-diamino-5-(5-carboxypentyl)-6-phenylphenanthridin-5-ium bromide
  参考文献：
  名称：

  Design, synthesis, and evaluation of phenanthridine derivatives targeting the telomerase RNA/DNA heteroduplex

  摘要：

  We are targeting molecules to the RNA/DNA heteroduplex that forms during the enzyme telomerase's catalytic cycle. Telomerase is a potential universal anti-cancer target that we have previously shown can be inhibited by molecules that target this heteroduplex. The aim of this work was to make derivatives of our lead, ethidium, that would allow its straightforward incorporation into molecules in both solid and solution phase. The heteroduplex targeting intercalator will act as a scaffold to allow the incorporation of new functionalities that will interact with specific protein surfaces of telomerase, thereby potentially increasing affinity and specificity. In examining multiple new derivatives of ethidium, with literature precedent or novel, we have identified one, a 5-benzylic acid ethidium derivative that is synthesized in three steps as a single isomer, and completely retains the inhibition efficacy of the parent compound. Furthermore, we have demonstrated that it can be effectively incorporated into resin bound amines on the solid phase. As such it represents an ideal monomer for the exploration of telomerse inhibition or for other applications which would benefit from hybrid molecules that can target duplexes. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.070
• 作为产物：
  描述：

  3,8-二氨基-6-苯基菲啶 在 吡啶 作用下， 以 硝基苯 为溶剂， 反应 24.0h， 生成 3,8-Bis(ethoxycarbonylamino)-5-(5-ethoxycarbonylpentyl)-6-phenylphenanthridinium trifluoromethanesulfonate
  参考文献：
  名称：

  Design, synthesis, and evaluation of phenanthridine derivatives targeting the telomerase RNA/DNA heteroduplex

  摘要：

  We are targeting molecules to the RNA/DNA heteroduplex that forms during the enzyme telomerase's catalytic cycle. Telomerase is a potential universal anti-cancer target that we have previously shown can be inhibited by molecules that target this heteroduplex. The aim of this work was to make derivatives of our lead, ethidium, that would allow its straightforward incorporation into molecules in both solid and solution phase. The heteroduplex targeting intercalator will act as a scaffold to allow the incorporation of new functionalities that will interact with specific protein surfaces of telomerase, thereby potentially increasing affinity and specificity. In examining multiple new derivatives of ethidium, with literature precedent or novel, we have identified one, a 5-benzylic acid ethidium derivative that is synthesized in three steps as a single isomer, and completely retains the inhibition efficacy of the parent compound. Furthermore, we have demonstrated that it can be effectively incorporated into resin bound amines on the solid phase. As such it represents an ideal monomer for the exploration of telomerse inhibition or for other applications which would benefit from hybrid molecules that can target duplexes. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.070

文献信息

• A straightforward preparation of primary alkyl triflates and their utility in the synthesis of derivatives of ethidium
  作者：Steven A. Ross、Marguerite Pitié、Bernard Meunier

  DOI：10.1039/a908389h

  日期：——

  The reaction of primary alcohols with trifluoromethanesulfonic anhydride in the presence of poly(4-vinylpyridine) [or poly(2,6-di-tert-butyl-4-vinylpyridine)] allows the isolation of the corresponding alkyl triflates in good yields. The quaternisation of 3,8-bis(ethoxycarbonylamino)-6-phenylphenanthridine (1) using these alkyl triflates was found to proceed smoothly at room temperature in nitrobenzene

  伯醇与三氟甲磺酸酐在聚（4-乙烯基吡啶）的存在下[或聚（2,6-二-反应叔丁基-4-乙烯基吡啶）]允许以良好的收率相应的烷基三氟甲磺酸酯的分离。发现使用这些烷基三氟甲磺酸酯对3,8-双（乙氧基羰基氨基）-6-苯基菲啶（1）的季铵化在室温下在硝基苯或氯苯中可顺利进行。已经发现，与先前报道的浓硫酸的使用相比，使用浓氢溴酸对这些季化合物进行脱保护是一种更有用的方法。据报道合成了新的乙啶衍生物3，8-二氨基-5-（5-氨基戊基）-6-苯基菲啶鎓溴化物（12）。
• Design, synthesis, and evaluation of phenanthridine derivatives targeting the telomerase RNA/DNA heteroduplex
  作者：Subhashree Rangarajan、Simon H. Friedman

  DOI：10.1016/j.bmcl.2007.01.070

  日期：2007.4

  We are targeting molecules to the RNA/DNA heteroduplex that forms during the enzyme telomerase's catalytic cycle. Telomerase is a potential universal anti-cancer target that we have previously shown can be inhibited by molecules that target this heteroduplex. The aim of this work was to make derivatives of our lead, ethidium, that would allow its straightforward incorporation into molecules in both solid and solution phase. The heteroduplex targeting intercalator will act as a scaffold to allow the incorporation of new functionalities that will interact with specific protein surfaces of telomerase, thereby potentially increasing affinity and specificity. In examining multiple new derivatives of ethidium, with literature precedent or novel, we have identified one, a 5-benzylic acid ethidium derivative that is synthesized in three steps as a single isomer, and completely retains the inhibition efficacy of the parent compound. Furthermore, we have demonstrated that it can be effectively incorporated into resin bound amines on the solid phase. As such it represents an ideal monomer for the exploration of telomerse inhibition or for other applications which would benefit from hybrid molecules that can target duplexes. (c) 2007 Elsevier Ltd. All rights reserved.