5-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1-phenylpyridin-2-one | 1349798-26-0

• 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: 5-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1-phenylpyridin-2-one
• CAS: 1349798-26-0
• 化学式: C₂₅H₂₈N₂O₂
• 分子量: 388.51
• InChiKey: BPQQIEBCWLLNSM-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-羟基苯硼酸频哪醇酯 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 sodium iodide 、 lithium chloride 作用下， 以 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 60.0h， 生成 5-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1-phenylpyridin-2-one
  参考文献：
  名称：

  Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists

  摘要：

  6-{4-[3-(R)-2-Methylpyrrolidin-1-yl) propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.091

文献信息

• Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists
  作者：Nadine C. Becknell、Jacquelyn A. Lyons、Lisa D. Aimone、John A. Gruner、Joanne R. Mathiasen、Rita Raddatz、Robert L. Hudkins

  DOI：10.1016/j.bmcl.2011.09.091

  日期：2011.12

  6-4-[3-(R)-2-Methylpyrrolidin-1-yl) propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H3R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H3R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H3R affinity. N-Methyl 9b showed excellent H3R affinity, acceptable pharmacokinetics and pharmaceutical properties. In vivo evaluation of 9b showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG model. (C) 2011 Elsevier Ltd. All rights reserved.