N-(2-(5-((4-(benzyloxy)cyclohexyl)oxy)-3'-fluoro-[1,1'-biphenyl]-2-yl)ethyl)acetamide | 1450643-46-5

• 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: N-(2-(5-((4-(benzyloxy)cyclohexyl)oxy)-3'-fluoro-[1,1'-biphenyl]-2-yl)ethyl)acetamide
• 英文别名: N-[2-[2-(3-fluorophenyl)-4-(4-phenylmethoxycyclohexyl)oxyphenyl]ethyl]acetamide
• CAS: 1450643-46-5
• 化学式: C₂₉H₃₂FNO₃
• 分子量: 461.576
• InChiKey: VBMJHAAMTRDGAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-(5-((4-(benzyloxy)cyclohexyl)oxy)-3'-fluoro-[1,1'-biphenyl]-2-yl)ethyl)acetamide 在 palladium on activated charcoal 、 氢气 作用下， 以100%的产率得到N-(2-(3'-fluoro-5-((4-hydroxycyclohexyl)oxy)-[1,1'-biphenyl]-2-yl)ethyl)acetamide
  参考文献：
  名称：

  Development of Noviomimetics as C-Terminal Hsp90 Inhibitors

  摘要：

  KU-32 and KU-596 are novobiocin-derived, C terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.

  DOI：

  10.1021/acsmedchemlett.5b00331
• 作为产物：
  描述：

  1,4-环己二醇 在 吡啶 、 sodium hydride 、 potassium carbonate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 32.5h， 生成 N-(2-(5-((4-(benzyloxy)cyclohexyl)oxy)-3'-fluoro-[1,1'-biphenyl]-2-yl)ethyl)acetamide
  参考文献：
  名称：

  [EN] C-TERMINAL HSP90 INHIBITORS
  [FR] INHIBITEURS DE HSP90 C-TERMINAUX

  摘要：

  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。

  公开号：

  WO2013119985A1

文献信息

• Development of noviomimetics that modulate molecular chaperones and manifest neuroprotective effects
  作者：Leah K. Forsberg、Mercy Anyika、Zhenyuan You、Sean Emery、Mason McMullen、Rick T. Dobrowsky、Brian S.J. Blagg

  DOI：10.1016/j.ejmech.2017.10.038

  日期：2018.1

  further explore the development of noviomimetics and evaluate their efficacy using a luciferase refolding assay, immunoblot analysis, a c-jun assay, and an assay measuring mitochondrial bioenergetics. These new noviomimetics were designed and synthesized and found to induce Hsp70 and improve biological activity. Noviomimetics 39e and 40a were found to induce Hsp70 and exhibit promising effects in cellular

  热休克蛋白90（Hsp90）是一种正在研究中的用于治疗癌症和神经退行性疾病的伴侣蛋白。衍生自新霉素（novologues）的神经保护性Hsp90 C-末端抑制剂包括KU-32和KU-596。这些创新分子调节分子伴侣，并导致热休克蛋白70（Hsp70）的诱导。与酚醛清毒剂KU-596和KU-32相比，“拟诺维制剂”用一个简单的环己基部分取代了合成复杂的酚醛新糖，以保持生物学功效。在这项研究中，我们进一步探索仿拟药物的开发，并使用荧光素酶复性测定，免疫印迹分析，c-jun测定和测量线粒体生物能的测定来评估其功效。这些新的仿拟药物是经过设计和合成的，可诱导Hsp70并改善其生物学活性。仿拟药物发现39e和40a在细胞测定中诱导Hsp70并显示出有希望的作用。
• 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。
• Biphenyl amides with modified ether groups as HSP90 inhibitors and HSP70 inducers
  申请人：THE UNIVERSITY OF KANSAS

  公开号：US10590065B2

  公开（公告）日：2020-03-17

  Provided herein are compounds of the formulas: (I) wherein: n, X2, R3, R3′, R4, R4′, R5, R5′, R6, and R6′ are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.

  本文提供的是式(I)的化合物：(I) 其中：n、X2、R3、R3′、R4、R4′、R5、R5′、R6 和 R6′ 如本文所定义。还提供了这些化合物的药物组合物。在某些方面，这些化合物可用于治疗疾病，包括糖尿病周围神经病变或癌症。