tert-butyl 4-[2-(1-naphthoyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-4-yl]piperazine-1-carboxylate | 1207461-29-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl 4-[2-(1-naphthoyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-4-yl]piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-[2-(naphthalene-1-carbonyl)-1-(2-trimethylsilylethoxymethyl)benzimidazol-4-yl]piperazine-1-carboxylate
• CAS: 1207461-29-7
• 化学式: C₃₃H₄₂N₄O₄Si
• 分子量: 586.806
• InChiKey: NKIVSRUTOHWHGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.79
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  76.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[2-(1-naphthoyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-4-yl]piperazine-1-carboxylate 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以64%的产率得到1-naphthyl(4-piperazin-1-yl-1H-benzimidazol-2-yl)methanone
  参考文献：
  名称：

  Benzimidazole Derivatives as New Serotonin 5-HT₆ Receptor Antagonists. Molecular Mechanisms of Receptor Inactivation

  摘要：

  On the basis of our previously described pharmacophore model for serotonin 5-HT6 receptor (5-HT6R) antagonists, we have designed, synthesized, and pharmacologically characterized a series of benzimidazole derivatives 1-20 that represent a new family of potent antagonists at the human 5-HT6R. Site-directed mutagenesis and a beta(2)-adrenoceptor-based homology model of the 5-HT6R were used to predict the mode of binding of antagonist SB-258585 and the new synthesized ligands. Substitution of W6.48, F6.52, or N6.55 by Ala fully impedes compound 4 to block 5-HT-induced activation. Thus, we propose that D3.32 in TM 3 anchors the protonated piperazine ring, the benzimidazole, ring expands parallel to EL 2 to hydrogen bond N6.55 in TM 6, and the aromatic ring is placed between TMs 3 and 5 in CH2-containing compounds and between TMs 3 and 6 in CO-containing compounds. This combined experimental and computational study has permitted to propose the molecular mechanisms by which the new benzimidazole derivatives act as 5-HT6R antagonists.

  DOI：

  10.1021/jm901672k
• 作为产物：
  描述：

  1-萘甲酸乙酯 、 tert-butyl 4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-4-yl)piperazine-1-carboxylate 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 以27%的产率得到tert-butyl 4-[2-(1-naphthoyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-4-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  Benzimidazole Derivatives as New Serotonin 5-HT₆ Receptor Antagonists. Molecular Mechanisms of Receptor Inactivation

  摘要：

  On the basis of our previously described pharmacophore model for serotonin 5-HT6 receptor (5-HT6R) antagonists, we have designed, synthesized, and pharmacologically characterized a series of benzimidazole derivatives 1-20 that represent a new family of potent antagonists at the human 5-HT6R. Site-directed mutagenesis and a beta(2)-adrenoceptor-based homology model of the 5-HT6R were used to predict the mode of binding of antagonist SB-258585 and the new synthesized ligands. Substitution of W6.48, F6.52, or N6.55 by Ala fully impedes compound 4 to block 5-HT-induced activation. Thus, we propose that D3.32 in TM 3 anchors the protonated piperazine ring, the benzimidazole, ring expands parallel to EL 2 to hydrogen bond N6.55 in TM 6, and the aromatic ring is placed between TMs 3 and 5 in CH2-containing compounds and between TMs 3 and 6 in CO-containing compounds. This combined experimental and computational study has permitted to propose the molecular mechanisms by which the new benzimidazole derivatives act as 5-HT6R antagonists.

  DOI：

  10.1021/jm901672k