(E)-2-[(4H-1,2,4-triazole-4-ylimino)-methyl]-4-chlorophenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-2-[(4H-1,2,4-triazole-4-ylimino)-methyl]-4-chlorophenol
• 英文别名: (E)-2-(((4H-1,2,4-triazol-4-yl)imino)methyl)-4-chlorophenol；4-Chloro-2-[(4H-1,2,4-triazol-4-ylimino)methyl]phenol；4-chloro-2-[(E)-1,2,4-triazol-4-yliminomethyl]phenol
• 化学式: C₉H₇ClN₄O
• 分子量: 222.634
• InChiKey: HFWTYWIOZCQUOE-YIXHJXPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-氨基-1,2,4-三氮唑 、 5-氯代水杨醛 以 乙醇 为溶剂， 反应 60.0h， 以88%的产率得到(E)-2-[(4H-1,2,4-triazole-4-ylimino)-methyl]-4-chlorophenol
  参考文献：
  名称：

  1,2,4-三唑胺及其氧杂钒（IV）配合物的衍生席夫碱配体的研究：合成，结构，DNA结合，碱性磷酸酶抑制，生物筛选和胰岛素模拟性质

  摘要：

  通过将4H-1,2,4-三唑-4-胺与水杨醛（HL 1）（saltrz），2,3-二羟基苯甲醛（HL 2）（dhtrz），2-缩合衍生化一系列新的甲亚胺前体羟基-1-萘醛（HL 3）（ndtrz）和5-氯-2-羟基苯甲醛（HL 4）（cltrz）。随后，[VO（saltrz）2 ]（1），[VO（dhtrz）2 ]（2），[VO（ndtrz）2 ]（3）和[VO（cltrz）2 ]（4）是通过异丙氧基钒（V）[VO（OCHMe2）3 ]与配体HL 1 - HL 4。通过熔点法，元素分析，FT-IR和1H和13 C NMR光谱，摩尔磁化率和电导率方法以及热重分析法对合成的化合物进行了表征。配体HL 3和HL 4还通过单晶分析表征。SS-DNA与化合物的结合模式已通过低色度和UV-Vis光谱的红/蓝位移证实。化合物-DNA加合物的DG负值表明结合是自发过程。发现该复合物是酶碱性磷酸酶（ALP）

  DOI：

  10.1134/s1070363215090248

文献信息

• 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
  作者：Iman Azimi、Jack U. Flanagan、Ralph J. Stevenson、Marco Inserra、Irina Vetter、Gregory R. Monteith、William A. Denny

  DOI：10.1016/j.bmc.2016.11.007

  日期：2017.1

  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.
• Investigation of derivatized schiff base ligands of 1,2,4-triazole amine and their oxovanadium(IV) complexes: Synthesis, structure, DNA binding, alkaline phosphatase inhibition, biological screening, and insulin mimetic properties
  作者：K. S. Munawar、S. Ali、M. N. Tahir、N. Khalid、Q. Abbas、I. Z. Qureshi、S. Shahzadi

  DOI：10.1134/s1070363215090248

  日期：2015.9

  e (HL 4) (cltrz). Subsequently, oxovanadium(IV) complexes of the type [VO(saltrz)2] (1), [VO(dhtrz)2] (2), [VO(ndtrz)2] (3), and [VO(cltrz)2] (4) were synthesized by the reactions of vanadyl(V) isopropoxide [VO(OCHMe2)3] with the ligands HL 1–HL 4. The synthesized compounds were characterized by the melting point method, elemental analysis, FT-IR and 1H and 13C NMR spectroscopies, the molar susceptibility

  通过将4H-1,2,4-三唑-4-胺与水杨醛（HL 1）（saltrz），2,3-二羟基苯甲醛（HL 2）（dhtrz），2-缩合衍生化一系列新的甲亚胺前体羟基-1-萘醛（HL 3）（ndtrz）和5-氯-2-羟基苯甲醛（HL 4）（cltrz）。随后，[VO（saltrz）2 ]（1），[VO（dhtrz）2 ]（2），[VO（ndtrz）2 ]（3）和[VO（cltrz）2 ]（4）是通过异丙氧基钒（V）[VO（OCHMe2）3 ]与配体HL 1 - HL 4。通过熔点法，元素分析，FT-IR和1H和13 C NMR光谱，摩尔磁化率和电导率方法以及热重分析法对合成的化合物进行了表征。配体HL 3和HL 4还通过单晶分析表征。SS-DNA与化合物的结合模式已通过低色度和UV-Vis光谱的红/蓝位移证实。化合物-DNA加合物的DG负值表明结合是自发过程。发现该复合物是酶碱性磷酸酶（ALP）