3-(1H-imidazol-4-yl)propyl 2-(2-chlorophenoxy)ethylcarbamate hydrogen maleate | 1450608-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(1H-imidazol-4-yl)propyl 2-(2-chlorophenoxy)ethylcarbamate hydrogen maleate
• 英文别名: 3-(1H-imidazol-5-yl)propyl N-[2-(2-chlorophenoxy)ethyl]carbamate
• CAS: 1450608-10-2
• 化学式: C₁₅H₁₈ClN₃O₃
• 分子量: 323.779
• InChiKey: MTCUDJGTLHSVNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(2-氯苯氧基)乙胺 在 charcoal 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 生成 3-(1H-imidazol-4-yl)propyl 2-(2-chlorophenoxy)ethylcarbamate hydrogen maleate
  参考文献：
  名称：

  Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol

  摘要：

  Ligands targeting central histamine H-3 receptors (H(3)Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H3R ligands 1-13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H3R ligand among 1-13, was significantly higher (P<0.05) than that of standard H3R antagonist THP, and was reversed when rats were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist Pyrilamine (PYR) (10 mg/kg). In addition, subeffective dose of H3R ligand 4 (5 mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5 mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H3R ligand 4 (10 mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H3R ligands 1-13 may be of future therapeutic value in epilepsy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.075

文献信息

• Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol
  作者：Bassem Sadek、Safa Shehab、Małgorzata Więcek、Dhanasekaran Subramanian、Mohamed Shafiullah、Katarzyna Kieć-Kononowicz、Abdu Adem

  DOI：10.1016/j.bmcl.2013.06.075

  日期：2013.9

  Ligands targeting central histamine H-3 receptors (H(3)Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H3R ligands 1-13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H3R ligand among 1-13, was significantly higher (P<0.05) than that of standard H3R antagonist THP, and was reversed when rats were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist Pyrilamine (PYR) (10 mg/kg). In addition, subeffective dose of H3R ligand 4 (5 mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5 mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H3R ligand 4 (10 mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H3R ligands 1-13 may be of future therapeutic value in epilepsy. (C) 2013 Elsevier Ltd. All rights reserved.