(E)-3-(4-((phenoxycarbonyl)amino)phenyl)acrylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-((phenoxycarbonyl)amino)phenyl)acrylic acid
• 英文别名: (E)-3-[4-(phenoxycarbonylamino)phenyl]prop-2-enoic acid
• 化学式: C₁₆H₁₃NO₄
• 分子量: 283.284
• InChiKey: SMVRPFYMMXUUGP-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((5-amino-1H-1,2,4-triazol-3-yl)amino)benzenesulfonamide 、 (E)-3-(4-((phenoxycarbonyl)amino)phenyl)acrylic acid 在 三乙胺 作用下， 以5%的产率得到(E)-3-(4-(5-amino-3-((4-sulfamoylphenyl)amino)-1H-1,2,4-triazole-1-carboxamido)phenyl)acrylic acid
  参考文献：
  名称：

  Selective JAK2 Pseudokinase Ligands and Methods of Use

  摘要：

  本文中描述的I式化合物通过特异性结合JAK2伪激酶结构域JH2来调节JAK2的活性，并可用作治疗或改善骨髓增生性疾病的治疗剂。此外，本文还提供了治疗骨髓增生性疾病的方法以及制备I式化合物的方法。

  公开号：

  US20220112166A1
• 作为产物：
  描述：

  (2E)-3-(4-氨基苯基)-2-丙烯酸 、 氯甲酸苯酯 在 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以53%的产率得到(E)-3-(4-((phenoxycarbonyl)amino)phenyl)acrylic acid
  参考文献：
  名称：

  Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core

  摘要：

  Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the discovery of molecules that may regulate the activity of JAK2 by selective binding to the JAK2 pseudokinase domain, JH2. Specifically, the Val617Phe mutation in JH2 stimulates the activity of the adjacent kinase domain (JH1) resulting in myeloproliferative disorders. Starting from a non-selective screening hit, we have achieved the goal of discovering molecules that preferentially bind to the ATP binding site in JH2 instead of JH1. We report the design and synthesis of the compounds and binding results for the JH1, JH2, and JH2 V617F domains, as well as five crystal structures for JH2 complexes. Testing with a selective and non-selective JH2 binder on the autophosphorylation of wild-type and V617F JAK2 is also contrasted.

  DOI：

  10.1021/acs.jmedchem.0c00192

文献信息

• Selective JAK2 Pseudokinase Ligands and Methods of Use
  申请人：YALE UNIVERSITY

  公开号：US20220112166A1

  公开（公告）日：2022-04-14

  The compounds of Formula I described herein regulate activity of JAK2 by specifically binding to the JAK2 pseudokinase domain, JH2, and are useful as therapeutic agents in the treatment or amelioration of myeloproliferative disorders. Also provided herein are methods of treating myeloproliferative disorders, and methods of making compounds of Formula I.

  本文中描述的I式化合物通过特异性结合JAK2伪激酶结构域JH2来调节JAK2的活性，并可用作治疗或改善骨髓增生性疾病的治疗剂。此外，本文还提供了治疗骨髓增生性疾病的方法以及制备I式化合物的方法。
• Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core
  作者：Maria-Elena Liosi、Stefan G. Krimmer、Ana S. Newton、Thomas K. Dawson、David E. Puleo、Kara J. Cutrona、Yoshihisa Suzuki、Joseph Schlessinger、William L. Jorgensen

  DOI：10.1021/acs.jmedchem.0c00192

  日期：2020.5.28

  Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the discovery of molecules that may regulate the activity of JAK2 by selective binding to the JAK2 pseudokinase domain, JH2. Specifically, the Val617Phe mutation in JH2 stimulates the activity of the adjacent kinase domain (JH1) resulting in myeloproliferative disorders. Starting from a non-selective screening hit, we have achieved the goal of discovering molecules that preferentially bind to the ATP binding site in JH2 instead of JH1. We report the design and synthesis of the compounds and binding results for the JH1, JH2, and JH2 V617F domains, as well as five crystal structures for JH2 complexes. Testing with a selective and non-selective JH2 binder on the autophosphorylation of wild-type and V617F JAK2 is also contrasted.