3-[(5-oxo-6,7,8,9-tetrahydrobenzo[7]annulen-2-yl)amino]-N-phenylbenzamide | 1395923-49-5

• 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: 3-[(5-oxo-6,7,8,9-tetrahydrobenzo[7]annulen-2-yl)amino]-N-phenylbenzamide
• CAS: 1395923-49-5
• 化学式: C₂₄H₂₂N₂O₂
• 分子量: 370.451
• InChiKey: DOPKQLKNNFLSNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-(3-chlorophenyl)pentanoic acid 在 aluminum (III) chloride 、 草酰氯 、 potassium tert-butylate 、 palladium diacetate 、 N,N-二甲基甲酰胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 5.0h， 生成 3-[(5-oxo-6,7,8,9-tetrahydrobenzo[7]annulen-2-yl)amino]-N-phenylbenzamide
  参考文献：
  名称：

  Targeting the Hinge Glycine Flip and the Activation Loop: Novel Approach to Potent p38α Inhibitors

  摘要：

  The p38 MAP kinase is a key player in signaling pathways regulating the biosynthesis of inflammatory cytokines. Small molecule p38 inhibitors suppress the production of these cytokines. Therefore p38 is a promising drug target for novel anti-inflammatory drugs. In this study, we report novel dibenzepinones, dibenzoxepines, and benzosuberones as p38 alpha MAP kinase inhibitors. Previously reported dibenzepinones and dibenzoxepines were chemically modified by introduction of functional groups or removal of a phenyl ring. This should result in targeting of the hydrophobic region I, the "deep pocket", and the hinge glycine flip of the kinase. Potent inhibitors with IC50 values in the single digit nanomolar range (up to 3 nM) were identified. Instead of targeting the "deep pocket" in the DFG-out conformation, interactions with the DFG-motif in the in-conformation could be observed by protein X-ray crystallography.

  DOI：

  10.1021/jm300951u

文献信息

• PROTEIN-PROTEIN INTERACTION MODULATORS OF AURORA KINASE A AND THEIR USE IN THE PREVENTION AND/OR TREATMENT OF CANCER
  申请人：Eberhard Karls Universität Tübingen

  公开号：EP3995494A1

  公开（公告）日：2022-05-11

  The present invention relates to compounds that modulate the conformation of Aurora Kinase A (AURKA). The compounds of the present invention are also modulators of the interactome of AURKA, and preferably alter the protein-protein interaction of AURKA with binding proteins, such as MYC and/or TPX2. The present invention also pertains to the use of such compounds in the prevention and/or treatment of proliferative diseases, such as cancer, and kits comprising the same.

  本发明涉及调节极化激酶A（AURKA）构象的化合物。本发明的化合物还是AURKA相互作用组的调节剂，并且优选地改变AURKA与结合蛋白（如MYC和/或TPX2）的蛋白质相互作用。本发明还涉及使用这种化合物预防和/或治疗增生性疾病，如癌症，以及包含这种化合物的试剂盒。
• Targeting the Hinge Glycine Flip and the Activation Loop: Novel Approach to Potent p38α Inhibitors
  作者：Kathrin E. Martz、Angelika Dorn、Benjamin Baur、Verena Schattel、Márcia I. Goettert、Svenja C. Mayer-Wrangowski、Daniel Rauh、Stefan A. Laufer

  DOI：10.1021/jm300951u

  日期：2012.9.13

  The p38 MAP kinase is a key player in signaling pathways regulating the biosynthesis of inflammatory cytokines. Small molecule p38 inhibitors suppress the production of these cytokines. Therefore p38 is a promising drug target for novel anti-inflammatory drugs. In this study, we report novel dibenzepinones, dibenzoxepines, and benzosuberones as p38 alpha MAP kinase inhibitors. Previously reported dibenzepinones and dibenzoxepines were chemically modified by introduction of functional groups or removal of a phenyl ring. This should result in targeting of the hydrophobic region I, the "deep pocket", and the hinge glycine flip of the kinase. Potent inhibitors with IC50 values in the single digit nanomolar range (up to 3 nM) were identified. Instead of targeting the "deep pocket" in the DFG-out conformation, interactions with the DFG-motif in the in-conformation could be observed by protein X-ray crystallography.