(E)-2-[(9-ethyl-9H-carbazol-3-yl)ethenyl]-quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-2-[(9-ethyl-9H-carbazol-3-yl)ethenyl]-quinoline
• 英文别名: (E)-2-[(9-ethyl-9H-carbazol-3-yl)ethenyl]quinoline；9-ethyl-3-[(E)-2-quinolin-2-ylethenyl]carbazole
• 化学式: C₂₅H₂₀N₂
• 分子量: 348.447
• InChiKey: BRPOFDDDQIAMHZ-SDNWHVSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  2-甲基喹啉 、 N-乙基咔唑-3-甲醛 在 乙酸酐 作用下， 反应 24.0h， 以67.1%的产率得到(E)-2-[(9-ethyl-9H-carbazol-3-yl)ethenyl]-quinoline
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimer's disease

  摘要：

  A series of new 2-arylethenylquinoline derivatives (4a(1)-4a(12), 4b(1)-4b(8), 4c(1)-4c(4), 4d(1)-4d(3) and 4e(1)-4e(9)) were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro studies showed that these synthetic compounds inhibited self-induced A beta(1-42) aggregation effectively ranged from 23.6% to 83.9% at the concentration of 20 mu M, and acted as potential antioxidants and biometal chelators. Their structure-activity relationships were obtained and discussed. In particular, compound 4b(1), the most active compound, displayed strong inhibitory activity with an IC50 value of 9.7 mu M for self-induced A beta(1-42) aggregation, good antioxidative activity with a value of 3.9-fold of Trolox, potent inhibitory activity for cholinesterase with IC50 values of 0.2 mu M and 64.1 mu M against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE), respectively. Besides, 4b(1) was also capable of disassembling the self-induced A beta(1-42) aggregation fibrils with a ratio of 59.8% at 20 mu M concentration, and had a good metal chelating activity. Taken together, these results suggest that compound 4b(1) might be a promising lead compound for AD treatment. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.018

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.
• [EN] METHODS FOR DYE SELECTION FOR PROTEIN MELT TEMPERATURE DETERMINATIONS<br/>[FR] PROCÉDÉS DE SÉLECTION DE COLORANTS POUR DES DÉTERMINATIONS DE TEMPÉRATURE DE FUSION DE PROTÉINES
  申请人：LIFE TECHNOLOGIES CORP

  公开号：WO2014144360A2

  公开（公告）日：2014-09-18

  According to the present teachings, compositions, kits, and methods for protein melt analysis are provided that utilizing one or more fluorophore dyes. In some embodiments, a method comprises preparing a sample by mixing at least one protein with two or more dyes, and applying a controlled heating, while recording the fluorescence emission of the sample. The methods can be used, for example, for screening conditions for optimized protein stability, screening for ligands that bind and enhance protein stability (e.g., protein-protein interactions), screening for mutations for enhanced stability, screening crystallization conditions for protein stability, screening storage conditions for protein stability, and screening conditions in which a protein will be used (e.g., production conditions, treatment conditions, etc.) for protein stability.
• Design, synthesis, and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimer's disease
  作者：Xiao-Qin Wang、Chun-Li Xia、Shuo-Bin Chen、Jia-Heng Tan、Tian-Miao Ou、Shi-Liang Huang、Ding Li、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.1016/j.ejmech.2014.10.018

  日期：2015.1

  A series of new 2-arylethenylquinoline derivatives (4a(1)-4a(12), 4b(1)-4b(8), 4c(1)-4c(4), 4d(1)-4d(3) and 4e(1)-4e(9)) were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro studies showed that these synthetic compounds inhibited self-induced A beta(1-42) aggregation effectively ranged from 23.6% to 83.9% at the concentration of 20 mu M, and acted as potential antioxidants and biometal chelators. Their structure-activity relationships were obtained and discussed. In particular, compound 4b(1), the most active compound, displayed strong inhibitory activity with an IC50 value of 9.7 mu M for self-induced A beta(1-42) aggregation, good antioxidative activity with a value of 3.9-fold of Trolox, potent inhibitory activity for cholinesterase with IC50 values of 0.2 mu M and 64.1 mu M against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE), respectively. Besides, 4b(1) was also capable of disassembling the self-induced A beta(1-42) aggregation fibrils with a ratio of 59.8% at 20 mu M concentration, and had a good metal chelating activity. Taken together, these results suggest that compound 4b(1) might be a promising lead compound for AD treatment. (C) 2014 Elsevier Masson SAS. All rights reserved.