4-chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)-1H-imidazole | 1193349-00-6

• 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: 4-chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)-1H-imidazole
• 英文别名: 4-Chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)imidazole；4-chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)imidazole
• CAS: 1193349-00-6
• 化学式: C₁₅H₆Cl₂F₄N₂
• 分子量: 361.126
• InChiKey: YPRQXMDCMYJQOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)-1H-imidazole 、 碘甲烷 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以13%的产率得到4-chloro-1-(4-chloro-3-fluorophenyl)-2-methyl-5-(2,3,6-trifluorophenyl)-1H-imidazole
  参考文献：
  名称：

  Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer’s and Other Neurodegenerative Diseases

  摘要：

  Alzheimer's disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and A beta species as well as neuroinflammation. In this context, the development of single multitargeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSALDs, we conducted structure-activity relationship studies that led to the identification of multitargeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several examples are brain-penetrant and exhibit balanced multitargeted in vitro activity in the low mu M range. As brain-penetrant MT-stabilizing agents have proven effective against tau-mediated neurodegeneration in animal models, and because COX- and 5-LOX-derived eicosanoids are thought to contribute to A beta plaque deposition, these 1,5-diarylimidazoles provide tools to explore novel multitargeted strategies for AD and other neurodegenerative diseases.

  DOI：

  10.1021/acs.jmedchem.7b00475
• 作为产物：
  描述：

  4-氯-3-氟苯胺 在 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 128.0h， 生成 4-chloro-1-(4-chloro-3-fluorophenyl)-5-(2,3,6-trifluorophenyl)-1H-imidazole
  参考文献：
  名称：

  Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer’s and Other Neurodegenerative Diseases

  摘要：

  Alzheimer's disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and A beta species as well as neuroinflammation. In this context, the development of single multitargeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSALDs, we conducted structure-activity relationship studies that led to the identification of multitargeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several examples are brain-penetrant and exhibit balanced multitargeted in vitro activity in the low mu M range. As brain-penetrant MT-stabilizing agents have proven effective against tau-mediated neurodegeneration in animal models, and because COX- and 5-LOX-derived eicosanoids are thought to contribute to A beta plaque deposition, these 1,5-diarylimidazoles provide tools to explore novel multitargeted strategies for AD and other neurodegenerative diseases.

  DOI：

  10.1021/acs.jmedchem.7b00475

文献信息

• [EN] MULTI-TARGETED HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES MULTI-CIBLE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV PENNSYLVANIA

  公开号：WO2018048969A1

  公开（公告）日：2018-03-15

  The present disclosure provides methods of treating neurodegenerative diseases, peripheral inflammatory conditions, cancers, or parasitic diseases in a subject, comprising administering to the subject a compound of Formula (I), (II), (III), and/or (IV):(I), (II), (III), (IV) or a pharmaceutically acceptable salt thereof, wherein X. R1-R8, R21-R28. R31-R38, and R41-R48 are as defined herein.

  本公开提供了治疗受试者的神经退行性疾病、外周炎症性疾病、癌症或寄生虫病的方法，包括向受试者施用式(I)、(II)、(III)和/或(IV)的化合物：(I)、(II)、(III)、(IV)或其药学上可接受的盐，其中X、R1-R8、R21-R28、R31-R38和R41-R48如本文所定义。
• Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer’s and Other Neurodegenerative Diseases
  作者：Anne-Sophie Cornec、Ludovica Monti、Jane Kovalevich、Vishruti Makani、Michael J. James、Krishna G. Vijayendran、Killian Oukoloff、Yuemang Yao、Virginia M.-Y. Lee、John Q. Trojanowski、Amos B. Smith、Kurt R. Brunden、Carlo Ballatore

  DOI：10.1021/acs.jmedchem.7b00475

  日期：2017.6.22

  Alzheimer's disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and A beta species as well as neuroinflammation. In this context, the development of single multitargeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSALDs, we conducted structure-activity relationship studies that led to the identification of multitargeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several examples are brain-penetrant and exhibit balanced multitargeted in vitro activity in the low mu M range. As brain-penetrant MT-stabilizing agents have proven effective against tau-mediated neurodegeneration in animal models, and because COX- and 5-LOX-derived eicosanoids are thought to contribute to A beta plaque deposition, these 1,5-diarylimidazoles provide tools to explore novel multitargeted strategies for AD and other neurodegenerative diseases.