4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-ethylphenyl)butan-1-one | 888472-02-4

• 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: 4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-ethylphenyl)butan-1-one
• 英文别名: 1-(4-Ethylphenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one；1-(4-ethylphenyl)-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butan-1-one
• CAS: 888472-02-4
• 化学式: C₃₀H₃₅NO₂
• 分子量: 441.613
• InChiKey: PUNWCEDDQDAMTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-ethylphenyl)butan-1-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以41%的产率得到4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-ethylphenyl)butan-1-ol
  参考文献：
  名称：

  Identification of Terfenadine as an Inhibitor of Human CD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization

  摘要：

  特非那定（4-[4-（羟二苯甲基）-1-哌啶基]-1-（4-叔丁基苯基）-丁烷-1-醇）在生物筛选中被识别为中等抑制剂（抑制率为27%），针对CD81-LEL与HCV-E2的相互作用。为了提高观察到的生物活性，通过微波辅助亲核取代合成了63个特非那定衍生物。这些制备的化合物通过使用HUH7.5细胞的荧光标记抗体检测法测试了它们的抑制效力。可以得出明显的结构-活性关系。优化取得了成功，导致了3g的识别，这是最强效的化合物（抑制率为69%）。对病毒颗粒的实验揭示可能存在额外的降低HCV感染的机制。

  DOI：

  10.3390/molecules13051081
• 作为产物：
  描述：

  乙基苯 生成 4-(4'-(hydroxy(diphenyl)methyl)piperidin-1-yl)-1-(4-ethylphenyl)butan-1-one
  参考文献：
  名称：

  Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2

  摘要：

  The active site topology, substrate specificity, and biological roles of the human cytochrome P450 CYP2J2, which is mainly expressed in the cardiovascular system, are poorly known even though recent data suggest that it Could be a novel biomarker and potential target for therapy of human cancer. This paper reports a first series of high-affinity, selective CYP2J2 inhibitors that are related to terfenadine, with K-i values as low as 160 nM, that should be useful tools to determine the biological roles of CYP2J2. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.02.004

文献信息

• US3965257A
  申请人：——

  公开号：US3965257A

  公开（公告）日：1976-06-22
• Identification of Terfenadine as an Inhibitor of Human CD81-Receptor HCV-E2 Interaction: Synthesis and Structure Optimization
  作者：Marcel Holzer、Sigrid Ziegler、Beatrice Albrecht、Bernd Kronenberger、Artur Kaul、Ralf Bartenschlager、Lars Kattner、Christian Klein、Rolf Hartmann

  DOI：10.3390/molecules13051081

  日期：——

  Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert-butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27% inhibition) of the CD81-LEL–HCV-E2 interaction. To increase the observed biologicalactivity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilicsubstitution. The prepared compounds were tested for their inhibitory potency by means ofa fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activityrelationships could be derived. Optimization was successful, leading to 3g, identfied as themost potent compound (69 % inhibition). Experiments with viral particles revealed thatthere might be additional HCV infection reducing mechanisms.

  特非那定（4-[4-（羟二苯甲基）-1-哌啶基]-1-（4-叔丁基苯基）-丁烷-1-醇）在生物筛选中被识别为中等抑制剂（抑制率为27%），针对CD81-LEL与HCV-E2的相互作用。为了提高观察到的生物活性，通过微波辅助亲核取代合成了63个特非那定衍生物。这些制备的化合物通过使用HUH7.5细胞的荧光标记抗体检测法测试了它们的抑制效力。可以得出明显的结构-活性关系。优化取得了成功，导致了3g的识别，这是最强效的化合物（抑制率为69%）。对病毒颗粒的实验揭示可能存在额外的降低HCV感染的机制。
• Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2
  作者：Pierre Lafite、Sylvie Dijols、Didier Buisson、Anne-Christine Macherey、Darryl C. Zeldin、Patrick M. Dansette、Daniel Mansuy

  DOI：10.1016/j.bmcl.2006.02.004

  日期：2006.5

  The active site topology, substrate specificity, and biological roles of the human cytochrome P450 CYP2J2, which is mainly expressed in the cardiovascular system, are poorly known even though recent data suggest that it Could be a novel biomarker and potential target for therapy of human cancer. This paper reports a first series of high-affinity, selective CYP2J2 inhibitors that are related to terfenadine, with K-i values as low as 160 nM, that should be useful tools to determine the biological roles of CYP2J2. (C) 2006 Elsevier Ltd. All rights reserved.