N-(2-(5-(benzyloxy)-2'-(methylthio)[1,1'-biphenyl]-2-yl)ethyl)acetamide | 1382723-09-2

• 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: N-(2-(5-(benzyloxy)-2'-(methylthio)[1,1'-biphenyl]-2-yl)ethyl)acetamide
• 英文别名: N-[2-[2-(2-methylsulfanylphenyl)-4-phenylmethoxyphenyl]ethyl]acetamide
• CAS: 1382723-09-2
• 化学式: C₂₄H₂₅NO₂S
• 分子量: 391.534
• InChiKey: PCMQZUKDGACDJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-(5-(benzyloxy)-2'-(methylthio)[1,1'-biphenyl]-2-yl)ethyl)acetamide 在 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 N-[2-(5-{[(3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-2'-(methylthio)-[1,1'-biphenyl]-2-yl)ethyl]acetamide
  参考文献：
  名称：

  Synthesis and Evaluation of Novologues as C-Terminal Hsp90 Inhibitors with Cytoprotective Activity against Sensory Neuron Glucotoxicity

  摘要：

  Compound 2 (KU-32) is a first-generation novologue (a novobiocin-based, C-terminal, heat shock protein 90 (Hsp90) inhibitor) that decreases glucose-induced death of primary sensory neurons and reverses numerous clinical indices of diabetic peripheral neuropathy in mice. The current study sought to exploit the C-terminal binding site of Hsp90 to determine whether the optimization of hydrogen bonding and hydrophobic interactions of second-generation novologues could enhance neuroprotective activity. Using a series of substituted phenylboronic acids to replace the coumarin lactone of 2, we identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket. Consistent with these results, a meta-3-fluorophenyl substituted novologue (13b) exhibited a 14-fold lower ED50 for protection against glucose-induced toxicity of primary sensory neurons compared to 2.

  DOI：

  10.1021/jm300544c
• 作为产物：
  描述：

  5-(苄氧基)-2-甲酰基苯基三氟甲磺酸酯 在 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 ammonium acetate 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 N-(2-(5-(benzyloxy)-2'-(methylthio)[1,1'-biphenyl]-2-yl)ethyl)acetamide
  参考文献：
  名称：

  Synthesis and Evaluation of Novologues as C-Terminal Hsp90 Inhibitors with Cytoprotective Activity against Sensory Neuron Glucotoxicity

  摘要：

  Compound 2 (KU-32) is a first-generation novologue (a novobiocin-based, C-terminal, heat shock protein 90 (Hsp90) inhibitor) that decreases glucose-induced death of primary sensory neurons and reverses numerous clinical indices of diabetic peripheral neuropathy in mice. The current study sought to exploit the C-terminal binding site of Hsp90 to determine whether the optimization of hydrogen bonding and hydrophobic interactions of second-generation novologues could enhance neuroprotective activity. Using a series of substituted phenylboronic acids to replace the coumarin lactone of 2, we identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket. Consistent with these results, a meta-3-fluorophenyl substituted novologue (13b) exhibited a 14-fold lower ED50 for protection against glucose-induced toxicity of primary sensory neurons compared to 2.

  DOI：

  10.1021/jm300544c

文献信息

• [EN] C-TERMINAL HSP90 INHIBITORS<br/>[FR] INHIBITEURS DE HSP90 C-TERMINAUX
  申请人：UNIV KANSAS

  公开号：WO2013119985A1

  公开（公告）日：2013-08-15

  Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.

  Hsp90 C端抑制剂及含有此类化合物的药物组合物。本发明公开的化合物可用于治疗和/或预防神经退行性疾病，如糖尿病周围神经病变。
• C-TERMINAL HSP90 INHIBITORS
  申请人：University of Kansas

  公开号：US20150057240A1

  公开（公告）日：2015-02-26

  Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.

  本文提供Hsp90 C-端抑制剂和含有这些化合物的药物组合物。本文所述的化合物对于治疗和/或预防神经退行性疾病，如糖尿病周围神经病变，非常有用。
• INTERMEDIATES FOR THE PREPARATION OF C-TERMINAL HSP90 INHIBITORS
  申请人：The University of Kansas

  公开号：EP3656758A1

  公开（公告）日：2020-05-27

  Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.

  本研究提供了 Hsp90 C-末端抑制剂和含有此类化合物的药物组合物。所公开的化合物可用于治疗和/或预防神经退行性疾病，如糖尿病周围神经病变。
• C-terminal Hsp90 inhibitors
  申请人：UNIVERSITY OF KANSAS

  公开号：US10030041B2

  公开（公告）日：2018-07-24

  Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.

  本研究提供了 Hsp90 C-末端抑制剂和含有此类化合物的药物组合物。所公开的化合物可用于治疗和/或预防神经退行性疾病，如糖尿病周围神经病变。
• C-terminal HSP90 inhibitors
  申请人：UNIVERSITY OF KANSAS

  公开号：US10590157B2

  公开（公告）日：2020-03-17

  Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.

  本研究提供了 Hsp90 C-末端抑制剂和含有此类化合物的药物组合物。所公开的化合物可用于治疗和/或预防神经退行性疾病，如糖尿病周围神经病变。