(E)-1-(2-(2-(4-(sec-butyl)phenoxy)ethoxy)-5-chlorophenyl)-N-(4H-1,2,4-triazol-4-yl)methanimine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-1-(2-(2-(4-(sec-butyl)phenoxy)ethoxy)-5-chlorophenyl)-N-(4H-1,2,4-triazol-4-yl)methanimine
• 英文别名: PqsR/LasR-IN-2；(E)-1-[2-[2-(4-butan-2-ylphenoxy)ethoxy]-5-chlorophenyl]-N-(1,2,4-triazol-4-yl)methanimine
• 化学式: C₂₁H₂₃ClN₄O₂
• 分子量: 398.892
• InChiKey: DLQFXDYTUCWLFI-DHRITJCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E)-2-[(4H-1,2,4-triazole-4-ylimino)-methyl]-4-chlorophenol 、 1-(2-bromoethoxy)-4-(sec-butyl)benzene 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以61%的产率得到(E)-1-(2-(2-(4-(sec-butyl)phenoxy)ethoxy)-5-chlorophenyl)-N-(4H-1,2,4-triazol-4-yl)methanimine
  参考文献：
  名称：

  Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca 2+ entry in MDA-MB-231 breast cancer cells using a Fluorescence Imaging Plate Reader assay

  摘要：

  The Orai1 Ca2+ permeable ion channel is an important component of store operated Ca2+ entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure-activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.11.007