VUF 5863

• 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: VUF 5863
• 英文别名: 4-(4-Chloro-phenyl)-1-(4-phenyl-4-p-tolyl-butyl)-piperidin-4-ol；4-(4-chlorophenyl)-1-[4-(4-methylphenyl)-4-phenylbutyl]piperidin-4-ol
• 化学式: C₂₈H₃₂ClNO
• 分子量: 434.021
• InChiKey: XQNMWCOBHLDKFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-甲基二苯甲烷 在 正丁基锂 、 sodium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 1.0h， 生成 VUF 5863
  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

文献信息

• Synthesis and Structure−Activity Relationship of the First Nonpeptidergic Inverse Agonists for the Human Cytomegalovirus Encoded Chemokine Receptor US28
  作者：Janneke W. Hulshof、Paola Casarosa、Wiro M. P. B. Menge、Leena M. S. Kuusisto、Henk van der Goot、Martine J. Smit、Iwan J. P. de Esch、Rob Leurs

  DOI：10.1021/jm050418d

  日期：2005.10.1

  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.