3-methyl-1-(4-(6-(piperidin-1-ylmethyl)pyridin-2-yl)benzyl)imidazolidine-2,4-dione | 1338056-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-methyl-1-(4-(6-(piperidin-1-ylmethyl)pyridin-2-yl)benzyl)imidazolidine-2,4-dione
• 英文别名: 3-Methyl-1-[[4-[6-(piperidin-1-ylmethyl)pyridin-2-yl]phenyl]methyl]imidazolidine-2,4-dione
• CAS: 1338056-01-1
• 化学式: C₂₂H₂₆N₄O₂
• 分子量: 378.474
• InChiKey: IPQGNHCGMASCIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-溴吡啶-2-甲醛 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 19.25h， 生成 3-methyl-1-(4-(6-(piperidin-1-ylmethyl)pyridin-2-yl)benzyl)imidazolidine-2,4-dione
  参考文献：
  名称：

  Discovery and Optimization of 1-(4-(Pyridin-2-yl)benzyl)imidazolidine-2,4-dione Derivatives As a Novel Class of Selective Cannabinoid CB2 Receptor Agonists

  摘要：

  Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (F-po = 4%) and possessed off-target activity at the hERG ion channel (pK(i), = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.0; hERG pK(i) < 4; F-po = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain.

  DOI：

  10.1021/jm200916p

文献信息

• Discovery and Optimization of 1-(4-(Pyridin-2-yl)benzyl)imidazolidine-2,4-dione Derivatives As a Novel Class of Selective Cannabinoid CB2 Receptor Agonists
  作者：Mario van der Stelt、Jos Cals、Silvia Broeders-Josten、Jean Cottney、Antoon A. van der Doelen、Marcel Hermkens、Vera de Kimpe、Angela King、Jan Klomp、Julia Oosterom、Ilse Pols-de Rooij、Jeroen de Roos、Martin van Tilborg、Susan Boyce、James Baker

  DOI：10.1021/jm200916p

  日期：2011.10.27

  Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (F-po = 4%) and possessed off-target activity at the hERG ion channel (pK(i), = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.0; hERG pK(i) < 4; F-po = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain.