5-(benzyloxy)acridone-4-carboxylic acid | 1187575-80-9

• 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: 5-(benzyloxy)acridone-4-carboxylic acid
• 英文别名: 9-oxo-5-phenylmethoxy-10H-acridine-4-carboxylic acid
• CAS: 1187575-80-9
• 化学式: C₂₁H₁₅NO₄
• 分子量: 345.354
• InChiKey: BHUHJTHJOQFALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基吡啶 、 5-(benzyloxy)acridone-4-carboxylic acid 在 吡啶 、 氯化亚砜 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以19%的产率得到5-benzyloxy-N-(pyridine-4-yl)-acridone-4-carboxamide
  参考文献：
  名称：

  Synthesis of New Acridone Derivatives, Inhibitors of NS3 Helicase, Which Efficiently and Specifically Inhibit Subgenomic HCV Replication

  摘要：

  A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 mu M). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC(50) of 3.5 and 1 mu M and therapeutic indexes of > 28 and 20, respectively. Compound 16, with EC(50) < 1 mu M and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs.

  DOI：

  10.1021/jm901741p
• 作为产物：
  描述：

  5-(benzyloxy)acridone-4-carboxylic acid benzyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以1.543 g的产率得到5-(benzyloxy)acridone-4-carboxylic acid
  参考文献：
  名称：

  [11C]-Elacridar 作为放射性示踪剂的合成和小动物正电子发射断层扫描评估 P-糖蛋白在血脑屏障的分布

  摘要：

  为了开发一种正电子发射断层扫描 (PET) 示踪剂来评估 P-糖蛋白 (P-gp) 在体内血脑屏障 (BBB) 的分布，有效的第三代 P-gp 抑制剂 elacridar ( 1 )通过O-去甲基1与[ 11 C]-三氟甲磺酸甲酯的反应用11 C标记。[ 11 C]- 1 的体外放射自显影和小动物 PET 成像在大鼠 ( n = 3) 中进行，在施用未标记的1之前和之后，以及在野生型Mdr1a/b (-/-)和Bcrp1 (-/-)小鼠 ( n= 3)。在大鼠的 PET 实验中，未标记的1 的给药使大脑活动吸收增加了 5.4 倍，而血液活动水平保持不变。在Mdr1a/b (-/-)小鼠中，与野生型动物相比，大脑活动摄取量高 2.5 倍，而在Bcrp1 (-/-)小鼠中，大脑活动摄取量仅高出 1.3 倍。体外放射自显影显示 63% 的 [ 11 C] -1结合可被过量的未标记1取代。由于用[

  DOI：

  10.1021/jm900940f

文献信息

• Synthesis and Small-Animal Positron Emission Tomography Evaluation of [¹¹C]-Elacridar As a Radiotracer to Assess the Distribution of P-Glycoprotein at the Blood−Brain Barrier
  作者：Bernd Dörner、Claudia Kuntner、Jens P. Bankstahl、Marion Bankstahl、Johann Stanek、Thomas Wanek、Gloria Stundner、Severin Mairinger、Wolfgang Löscher、Markus Müller、Oliver Langer、Thomas Erker

  DOI：10.1021/jm900940f

  日期：2009.10.8

  With the aim to develop a positron emission tomography (PET) tracer to assess the distribution of P-glycoprotein (P-gp) at the blood−brain barrier (BBB) in vivo, the potent third-generation P-gp inhibitor elacridar (1) was labeled with 11C by reaction of O-desmethyl 1 with [11C]-methyl triflate. In vitro autoradiography and small-animal PET imaging of [11C]-1 was performed in rats (n = 3), before and

  为了开发一种正电子发射断层扫描 (PET) 示踪剂来评估 P-糖蛋白 (P-gp) 在体内血脑屏障 (BBB) 的分布，有效的第三代 P-gp 抑制剂 elacridar ( 1 )通过O-去甲基1与[ 11 C]-三氟甲磺酸甲酯的反应用11 C标记。[ 11 C]- 1 的体外放射自显影和小动物 PET 成像在大鼠 ( n = 3) 中进行，在施用未标记的1之前和之后，以及在野生型Mdr1a/b (-/-)和Bcrp1 (-/-)小鼠 ( n= 3)。在大鼠的 PET 实验中，未标记的1 的给药使大脑活动吸收增加了 5.4 倍，而血液活动水平保持不变。在Mdr1a/b (-/-)小鼠中，与野生型动物相比，大脑活动摄取量高 2.5 倍，而在Bcrp1 (-/-)小鼠中，大脑活动摄取量仅高出 1.3 倍。体外放射自显影显示 63% 的 [ 11 C] -1结合可被过量的未标记1取代。由于用[
• Synthesis of New Acridone Derivatives, Inhibitors of NS3 Helicase, Which Efficiently and Specifically Inhibit Subgenomic HCV Replication
  作者：Anna Stankiewicz-Drogoń、Bernd Dörner、Thomas Erker、Anna M. Boguszewska-Chachulska

  DOI：10.1021/jm901741p

  日期：2010.4.22

  A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 mu M). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC(50) of 3.5 and 1 mu M and therapeutic indexes of > 28 and 20, respectively. Compound 16, with EC(50) < 1 mu M and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs.