2-[4-[(3-Fluorophenyl)carbamoyl]naphthalen-1-yl]oxyacetic acid | 745821-86-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[4-[(3-Fluorophenyl)carbamoyl]naphthalen-1-yl]oxyacetic acid
• CAS: 745821-86-7
• 化学式: C₁₉H₁₄FNO₄
• 分子量: 339.323
• InChiKey: TZESLSHMDPKGJN-UHFFFAOYSA-N

物化性质

• 沸点：
  481.3±35.0 °C(Predicted)
• 密度：
  1.403±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-[(3-Fluorophenyl)carbamoyl]naphthalen-1-yl]oxyacetic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氨 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.0h， 以90%的产率得到4-Carbamoylmethoxy-naphthalene-1-carboxylic acid (3-fluoro-phenyl)-amide
  参考文献：
  名称：

  Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds

  摘要：

  本发明涉及1,4-二取代萘骨架化合物及其他密切相关的骨架化合物。本发明还涉及这些化合物的组合式库。此外，本发明涉及一种鉴定蛋白质-蛋白质相互作用拮抗剂的方法。该方法首先涉及提供本文描述的化合物。接下来，将该化合物与蛋白质-蛋白质相互作用目标复合物的相互作用蛋白质接触，使该化合物能够与相互作用蛋白质竞争。然后，测量该化合物抑制蛋白质-蛋白质相互作用目标复合物形成的活性。最后，确定抑制蛋白质-蛋白质相互作用目标复合物形成的化合物为蛋白质-蛋白质相互作用拮抗剂。还公开了一种调节蛋白质-蛋白质相互作用的方法。该方法涉及将本文描述的化合物与蛋白质-蛋白质相互作用目标的相互作用蛋白质接触，从而调节相互作用蛋白质之间的蛋白质-蛋白质相互作用。

  公开号：

  US20050153366A1
• 作为产物：
  描述：

  4-甲氧基-1-萘酸氯 在 lithium hydroxide 、 三氯化铝 、 potassium carbonate 、 N,N-二异丙基乙胺 、 乙硫醇 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-[4-[(3-Fluorophenyl)carbamoyl]naphthalen-1-yl]oxyacetic acid
  参考文献：
  名称：

  Privileged scaffolds for blocking protein–protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX–PBX/DNA

  摘要：

  Structure-based-design studies, with the crystal structure of the HOXB1-PBX1/DNA transcription factor complex, were used to identify 1,4-disubstituted naphthalenes as potential antagonists. An initial library of 32 analogs was synthesized, two of which were found to be more potent than the reported activity for a 12 amino acid peptide antagonist. Antagonists were also identified of the related BRN1/DNA and BRN2/DNA transcription factor complexes indicating that a 1,4-disubsituted naphthalene may be a privileged scaffold for preparing screening libraries targeting this family of transcription factor complexes. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.068

文献信息

• US7662750B2
  申请人：——

  公开号：US7662750B2

  公开（公告）日：2010-02-16
• Protein-protein interaction antagonist screening libraries based upon 1,4-disubstituted naphthalenes and related scaffolds
  申请人：Hangauer G. David

  公开号：US20050153366A1

  公开（公告）日：2005-07-14

  The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.

  本发明涉及1,4-二取代萘骨架化合物及其他密切相关的骨架化合物。本发明还涉及这些化合物的组合式库。此外，本发明涉及一种鉴定蛋白质-蛋白质相互作用拮抗剂的方法。该方法首先涉及提供本文描述的化合物。接下来，将该化合物与蛋白质-蛋白质相互作用目标复合物的相互作用蛋白质接触，使该化合物能够与相互作用蛋白质竞争。然后，测量该化合物抑制蛋白质-蛋白质相互作用目标复合物形成的活性。最后，确定抑制蛋白质-蛋白质相互作用目标复合物形成的化合物为蛋白质-蛋白质相互作用拮抗剂。还公开了一种调节蛋白质-蛋白质相互作用的方法。该方法涉及将本文描述的化合物与蛋白质-蛋白质相互作用目标的相互作用蛋白质接触，从而调节相互作用蛋白质之间的蛋白质-蛋白质相互作用。
• Privileged scaffolds for blocking protein–protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX–PBX/DNA
  作者：Tao Ji、Madison Lee、Steven C. Pruitt、David G. Hangauer

  DOI：10.1016/j.bmcl.2004.05.068

  日期：2004.8

  Structure-based-design studies, with the crystal structure of the HOXB1-PBX1/DNA transcription factor complex, were used to identify 1,4-disubstituted naphthalenes as potential antagonists. An initial library of 32 analogs was synthesized, two of which were found to be more potent than the reported activity for a 12 amino acid peptide antagonist. Antagonists were also identified of the related BRN1/DNA and BRN2/DNA transcription factor complexes indicating that a 1,4-disubsituted naphthalene may be a privileged scaffold for preparing screening libraries targeting this family of transcription factor complexes. (C) 2004 Elsevier Ltd. All rights reserved.