2-(hexylthio)-6-methylpyrimidin-4-ol | 138468-63-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(hexylthio)-6-methylpyrimidin-4-ol
• 英文别名: 2-(Hexylthio)-6-methylpyrimidin-4(1H)-one；2-hexylsulfanyl-4-methyl-1H-pyrimidin-6-one
• CAS: 138468-63-0
• 化学式: C₁₁H₁₈N₂OS
• mdl: MFCD02333740
• 分子量: 226.343
• InChiKey: BVHSWWDTJRBRKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  溴己烷 、 甲基硫脲嘧啶 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 2-(hexylthio)-6-methylpyrimidin-4-ol
  参考文献：
  名称：

  An Agonist Radioligand for the Proinflammatory Lipid-Activated G Protein-Coupled Receptor GPR84 Providing Structural Insights

  摘要：

  The orphan G protein-coupled receptor (GPCR) GPR84 is expressed on immune cells mediating proinflammatory and immunostimulatory effects. In this study, we prepared the fully efficacious, nonbiased GPR84 agonist 6-hexylamino-2,4(1H,3H)-pyrimidinedione (6) in tritium-labeled form ([H-3]PSB-1584) by hydrogenation of a hexenyl-substituted precursor with tritium gas. The radio-ligand was characterized by kinetic, saturation, and competition assays using membranes of Chinese hamster ovary cells recombinantly expressing the human GPR84. [H-3]6 reversibly labeled the receptor with high affinity (K-D 2.08 nM). Structurally diverse orthosteric and allosteric ligands, including newly designed and synthesized compounds, were studied in competition binding assays. A homology model of GPR84 was generated to perform docking studies rationalizing the experimental data. The radioligand was additionally used for labeling GPR84 in native cells and tissues. [H-3]6 constitutes the first GPR84 agonist radioligand representing a powerful tool for this poorly investigated GPCR, which has potential as a future drug target.

  DOI：

  10.1021/acs.jmedchem.9b01339

文献信息

• An Agonist Radioligand for the Proinflammatory Lipid-Activated G Protein-Coupled Receptor GPR84 Providing Structural Insights
  作者：Meryem Köse、Thanigaimalai Pillaiyar、Vigneshwaran Namasivayam、Elisabetta De Filippo、Katharina Sylvester、Trond Ulven、Ivar von Kügelgen、Christa E. Müller

  DOI：10.1021/acs.jmedchem.9b01339

  日期：2020.3.12

  The orphan G protein-coupled receptor (GPCR) GPR84 is expressed on immune cells mediating proinflammatory and immunostimulatory effects. In this study, we prepared the fully efficacious, nonbiased GPR84 agonist 6-hexylamino-2,4(1H,3H)-pyrimidinedione (6) in tritium-labeled form ([H-3]PSB-1584) by hydrogenation of a hexenyl-substituted precursor with tritium gas. The radio-ligand was characterized by kinetic, saturation, and competition assays using membranes of Chinese hamster ovary cells recombinantly expressing the human GPR84. [H-3]6 reversibly labeled the receptor with high affinity (K-D 2.08 nM). Structurally diverse orthosteric and allosteric ligands, including newly designed and synthesized compounds, were studied in competition binding assays. A homology model of GPR84 was generated to perform docking studies rationalizing the experimental data. The radioligand was additionally used for labeling GPR84 in native cells and tissues. [H-3]6 constitutes the first GPR84 agonist radioligand representing a powerful tool for this poorly investigated GPCR, which has potential as a future drug target.