2-(4-{[2-(3-ethylphenoxy)ethyl]amino}butyl)tetrahydro-1Hpyrrolo[1,2-c]imidazole-1,3(2H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2-(4-{[2-(3-ethylphenoxy)ethyl]amino}butyl)tetrahydro-1Hpyrrolo[1,2-c]imidazole-1,3(2H)-dione
• 英文别名: 2-[4-[2-(4-Ethylphenoxy)ethylamino]butyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione；2-[4-[2-(4-ethylphenoxy)ethylamino]butyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• 化学式: C₂₀H₂₉N₃O₃
• 分子量: 359.469
• InChiKey: AXELRQFGUJCERL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-乙基苯酚 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 、 丁酮 为溶剂， 反应 63.0h， 生成 2-(4-{[2-(3-ethylphenoxy)ethyl]amino}butyl)tetrahydro-1Hpyrrolo[1,2-c]imidazole-1,3(2H)-dione
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists Endowed with Antinociceptive Activity in Vivo

  摘要：

  We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-{[2-(2-ethoxyphenoxy)ethyl]amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione] has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t(1/2) similar to 3 h and CLint = 3.5 mL/min/kg, at 5 mu M), and a low level of protein binding (25%, at 5 mu M). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.

  DOI：

  10.1021/jm400766k

文献信息

• New Serotonin 5-HT_1A Receptor Agonists Endowed with Antinociceptive Activity <i>in Vivo</i>
  作者：Margarita Valhondo、Isabel Marco、Mar Martín-Fontecha、Henar Vázquez-Villa、José A. Ramos、Reinhard Berkels、Thomas Lauterbach、Bellinda Benhamú、María L. López-Rodríguez

  DOI：10.1021/jm400766k

  日期：2013.10.24

  We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-[2-(2-ethoxyphenoxy)ethyl]amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione] has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t(1/2) similar to 3 h and CLint = 3.5 mL/min/kg, at 5 mu M), and a low level of protein binding (25%, at 5 mu M). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.