6-(4-ethylpiperazin-1-yl)-5-methyl-1-[2-(trimethylsilyl)-ethoxymethyl]benzimidazole | 626238-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(4-ethylpiperazin-1-yl)-5-methyl-1-[2-(trimethylsilyl)-ethoxymethyl]benzimidazole
• 英文别名: 2-[[6-(4-Ethylpiperazin-1-yl)-5-methylbenzimidazol-1-yl]methoxy]ethyl-trimethylsilane
• CAS: 626238-83-3
• 化学式: C₂₀H₃₄N₄OSi
• 分子量: 374.602
• InChiKey: NIQMNQYSRFALPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  33.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  、 2-(三甲基硅烷基)乙氧甲基氯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 6-(4-ethylpiperazin-1-yl)-5-methyl-1-[2-(trimethylsilyl)-ethoxymethyl]benzimidazole 、 5-(4-ethylpiperazin-1-yl)-6-methyl-1-[2-(trimethylsilyl) ethoxymethyl]benzimidazole
  参考文献：
  名称：

  2-Cyclohexylcarbonylbenzimidazoles as potent, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonists

  摘要：

  The synthesis and biological evaluation of new potent opioid receptor-like 1 (ORL1) antagonists are presented. Conversion of the thioether linkage of the prototype [It is reported prior to this communication as a consecutive series.: Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.; Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto, O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited potent ORL1 activity, excellent selectivity over other receptors and ion channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a clinical candidate for a brain-penetrable ORL1 antagonist. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.023