3-[(叔丁氧基羰基)氨基]-1,1-联苯-4-羧酸 | 904086-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-[(叔丁氧基羰基)氨基]-1,1-联苯-4-羧酸
• 英文名称: 3'-[[(1,1-dimethylethoxy)carbonyl]amino][1,1'-biphenyl]-4-carboxylic acid
• 英文别名: 3'-((tert-Butoxycarbonyl)amino)-[1,1'-biphenyl]-4-carboxylic acid；4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]benzoic acid
• CAS: 904086-02-8
• 化学式: C₁₈H₁₉NO₄
• 分子量: 313.353
• InChiKey: HAEPMXWZNSSFAB-UHFFFAOYSA-N

物化性质

• 沸点：
  449.9±38.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  3-[(叔丁氧基羰基)氨基]-1,1-联苯-4-羧酸 在 对甲酚 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 3'-[N-[(1,1-dimethylethoxy)carbonyl]-L-tryptophylamino][1,1'-biphenyl]-4-carbonyl-L-phenylalanine methyl ester
  参考文献：
  名称：

  Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand

  摘要：

  Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA: uPAR interaction represent promising antitumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC50 1 = 0.8 nM, IC50 2 = 33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 mu M) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 mu M. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC50 > 100 mu M for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.016
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 3-氨基-联苯-4-羧酸 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以99%的产率得到3-[(叔丁氧基羰基)氨基]-1,1-联苯-4-羧酸
  参考文献：
  名称：

  Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand

  摘要：

  Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA: uPAR interaction represent promising antitumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC50 1 = 0.8 nM, IC50 2 = 33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 mu M) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 mu M. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC50 > 100 mu M for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.016

文献信息

• NEUROMEDIN U DERIVATIVE
  申请人：Ohtaki Tetsuya

  公开号：US20100286035A1

  公开（公告）日：2010-11-11

  The objective of the present invention is to provide a new antifeedant. The other objective of the present invention is to provide a NMU derivative showing a high antifeedant activity even in common administration forms such as peripheral administration. A neuromedin U derivative wherein a methoxypolyethylene glycol is bound via a linker having a specific structure to a polypeptide which contains at least 8 amino acids of the C-terminus of an amino acid sequence of neuromedin U and which consists of the same or substantially the same amino acid sequence as the amino acid sequence of neuromedin U.

  本发明的目的是提供一种新的抗饲料剂。本发明的另一个目的是提供一种NMU衍生物，即使在常见的给药形式如周围给药中也表现出高抗饲料活性。一种神经介质U衍生物，其中通过具有特定结构的连接物将甲氧基聚乙二醇与包含神经介质U氨基酸序列C-末端至少8个氨基酸的多肽结合，该多肽由与神经介质U氨基酸序列相同或基本相同的氨基酸序列组成。
• Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand
  作者：Melissa De Souza、Hayden Matthews、Jodi A. Lee、Marie Ranson、Michael J. Kelso

  DOI：10.1016/j.bmc.2011.03.016

  日期：2011.4

  Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA: uPAR interaction represent promising antitumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC50 1 = 0.8 nM, IC50 2 = 33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 mu M) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 mu M. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC50 > 100 mu M for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. (C) 2011 Elsevier Ltd. All rights reserved.