(E)-2-(2-hydroxy-5-nitrostyryl)-1-methyl-4-(piperidin-1-yl)quinolin-1-ium iodide

• 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: (E)-2-(2-hydroxy-5-nitrostyryl)-1-methyl-4-(piperidin-1-yl)quinolin-1-ium iodide
• 英文别名: 2-[(E)-2-(1-methyl-4-piperidin-1-ylquinolin-1-ium-2-yl)ethenyl]-4-nitrophenol;iodide
• 化学式: C₂₃H₂₄N₃O₃*I
• 分子量: 517.366
• InChiKey: DRTBXSMADVSCHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.44
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-羟基-2-甲基喹啉 在 环丁砜 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (E)-2-(2-hydroxy-5-nitrostyryl)-1-methyl-4-(piperidin-1-yl)quinolin-1-ium iodide
  参考文献：
  名称：

  Discovery of Small Molecules for Up-Regulating the Translation of Antiamyloidogenic Secretase, a Disintegrin and Metalloproteinase 10 (ADAM10), by Binding to the G-Quadruplex-Forming Sequence in the 5′ Untranslated Region (UTR) of Its mRNA

  摘要：

  Up-regulation of a disintegrin and metalloptoteinase 10 (ADAM10) to prevent the formation of beta-amyloid (A beta) peptides might be a promising strategy to treat Alzheimer's disease (AD). RNA G-quadruplex motif within the 5'-UTR of the ADAM10 mRNA is an inhibitory element for ADAM10 translation. Thus, mitigation of the suppressive effect of this motif using an RNA G-quadruplex-forming G-rich sequence (QGRS) binder might be a new approach for AD therapy. Herein, a series of new methylquinolinium derivatives were synthesized and screened by surface plasmon resonance (SPR) and the dual-luciferase reporter assay. Among them, compound 24 showed selective affinity for the QGRS of ADAM10 and could strongly up-regulate the translation of it. Moreover, treatment with 24 led to a significant increase of the secretion of sAPP alpha, consequently decreasing the A beta(40) in cellular. These results illustrate that the ititeraction between the RNA QGRS and a small molecule may be a new molecular strategy to modulate the translation of ADAM10.

  DOI：

  10.1021/acs.jmedchem.5b00139

文献信息

• Discovery of Small Molecules for Up-Regulating the Translation of Antiamyloidogenic Secretase, a Disintegrin and Metalloproteinase 10 (ADAM10), by Binding to the G-Quadruplex-Forming Sequence in the 5′ Untranslated Region (UTR) of Its mRNA
  作者：Jie Dai、Zhen-Quan Liu、Xiao-Qin Wang、Jing Lin、Pei-Fen Yao、Shi-Liang Huang、Tian-Miao Ou、Jia-Heng Tan、Ding Li、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.1021/acs.jmedchem.5b00139

  日期：2015.5.14

  Up-regulation of a disintegrin and metalloptoteinase 10 (ADAM10) to prevent the formation of beta-amyloid (A beta) peptides might be a promising strategy to treat Alzheimer's disease (AD). RNA G-quadruplex motif within the 5'-UTR of the ADAM10 mRNA is an inhibitory element for ADAM10 translation. Thus, mitigation of the suppressive effect of this motif using an RNA G-quadruplex-forming G-rich sequence (QGRS) binder might be a new approach for AD therapy. Herein, a series of new methylquinolinium derivatives were synthesized and screened by surface plasmon resonance (SPR) and the dual-luciferase reporter assay. Among them, compound 24 showed selective affinity for the QGRS of ADAM10 and could strongly up-regulate the translation of it. Moreover, treatment with 24 led to a significant increase of the secretion of sAPP alpha, consequently decreasing the A beta(40) in cellular. These results illustrate that the ititeraction between the RNA QGRS and a small molecule may be a new molecular strategy to modulate the translation of ADAM10.