4-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)phenol | 1191288-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)phenol
• 英文别名: 4-(4-(Pyridin-3-yl)-1h-1,2,3-triazol-1-yl) phenol；4-(4-pyridin-3-yltriazol-1-yl)phenol
• CAS: 1191288-81-9
• 化学式: C₁₃H₁₀N₄O
• 分子量: 238.249
• InChiKey: YGNSZPMASIQLDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 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：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 4-(4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)phenol
  参考文献：
  名称：

  Receptor agonists of macrophage migration inhibitory factor

  摘要：

  The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also promotes AMPK activation with potential benefits for response to myocardial infarction and ischemia-reperfusion. Structure-based molecular design has led to the discovery of not only antagonists, but also the first agonists of MIF-CD74 binding. The compounds contain a triazole core that is readily assembled via Cu-catalyzed click chemistry. The agonist and antagonist behaviors were confirmed via study of MIF-dependent ERK1/2 phosphorylation in human fibroblasts. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.118

文献信息

• Design, Synthesis, and Protein Crystallography of Biaryltriazoles as Potent Tautomerase Inhibitors of Macrophage Migration Inhibitory Factor
  作者：Pawel Dziedzic、José A. Cisneros、Michael J. Robertson、Alissa A. Hare、Nadia E. Danford、Richard H. G. Baxter、William L. Jorgensen

  DOI：10.1021/ja512112j

  日期：2015.3.4

  Optimization is reported for biaryltriazoles as inhibitors of the tautomerase activity of human macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with numerous inflammatory diseases and cancer. A combined approach was taken featuring organic synthesis, enzymatic assaying, crystallography, and modeling including free-energy perturbation (FEP) calculations. X-ray crystal

  据报道，联芳基三唑可作为人类巨噬细胞迁移抑制因子 (MIF) 互变异构酶活性的抑制剂进行优化，MIF 是一种与多种炎症疾病和癌症相关的促炎细胞因子。采用有机合成、酶分析、晶体学和建模（包括自由能扰动 (FEP) 计算）的组合方法。报告了与 MIF 结合的 3a 和 3b 的 X 射线晶体结构，并为建模工作提供了基础。抑制剂在结合位点的适应以多个氢键和芳基-芳基相互作用而引人注目。额外的建模鼓励了对 5-苯氧基喹啉基类似物的探索，这导致了非常有效的化合物 3s。通过添加与酚羟基相邻的氟原子进一步增强活性，如 3w、3z、3aa 和 3bb 以加强关键的氢键。还表明，化合物的物理性质可以通过溶剂暴露取代基的变化来调节。其中一些化合物可能是已知最有效的 MIF 互变异构酶抑制剂；最活跃的比经过充分研究的 (R)-ISO-1 活跃 1000 多倍，比 chromen-4-one Orita-13 活跃
• [EN] COMPOUNDS AND METHODS FOR TREATING COPD AND/OR LUNG FIBROSIS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT D'UNE MPOC ET/OU D'UNE FIBROSE PULMONAIRE
  申请人：UNIV YALE

  公开号：WO2020123610A1

  公开（公告）日：2020-06-18

  In various aspects and embodiments the invention provides methods for the treatment of a MIF-mediated disease. In one aspect, the invention provides a method of treating a fibrotic disease in a male subject in need thereof, the method comprising administering to the male subject an effective amount of at least one MIF agonist. In various embodiments, the fibrotic disease is lung fibrosis. In another aspect, the invention provides a method of treating chronic obstructive pulmonary disease (COPD) in a female subject in need thereof, the method comprising administering to the female subject an effective amount of at least one MIF agonist. In various embodiments, the COPD is emphysema type COPD.
• Receptor agonists of macrophage migration inhibitory factor
  作者：William L. Jorgensen、Sunilkumar Gandavadi、Xin Du、Alissa A. Hare、Alexander Trofimov、Lin Leng、Richard Bucala

  DOI：10.1016/j.bmcl.2010.09.118

  日期：2010.12

  The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also promotes AMPK activation with potential benefits for response to myocardial infarction and ischemia-reperfusion. Structure-based molecular design has led to the discovery of not only antagonists, but also the first agonists of MIF-CD74 binding. The compounds contain a triazole core that is readily assembled via Cu-catalyzed click chemistry. The agonist and antagonist behaviors were confirmed via study of MIF-dependent ERK1/2 phosphorylation in human fibroblasts. (C) 2010 Elsevier Ltd. All rights reserved.