[4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-phenylbutyl] acetate | 868607-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-phenylbutyl] acetate
• CAS: 868607-41-4
• 化学式: C₂₃H₂₈ClNO₃
• 分子量: 401.933
• InChiKey: UGUMSVQZCIMHSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-phenylbutyl] acetate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以41%的产率得到4-(4-chlorophenyl)-1-(4-hydroxy-4-phenylbutyl)piperidin-4-ol
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of the First Nonpeptidergic Inverse Agonists for the Human Cytomegalovirus Encoded Chemokine Receptor US28

  摘要：

  US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 {5-(4-(4-chlorophenyl)-4-hydroxy-piperidin-1-yl)-2,2-diphenylpentanenitrile} as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

  DOI：

  10.1021/jm050418d
• 作为产物：
  描述：

  4-chloro-1-phenylbutan-1-ol 在 sodium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 1.0h， 生成 [4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-phenylbutyl] acetate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of the First Nonpeptidergic Inverse Agonists for the Human Cytomegalovirus Encoded Chemokine Receptor US28

  摘要：

  US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 {5-(4-(4-chlorophenyl)-4-hydroxy-piperidin-1-yl)-2,2-diphenylpentanenitrile} as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

  DOI：

  10.1021/jm050418d