2-[4-(3-Chloro-phenyl)-piperazin-1-ylmethyl]-1H-benzoimidazole

• 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: 2-[4-(3-Chloro-phenyl)-piperazin-1-ylmethyl]-1H-benzoimidazole
• 英文别名: Dopamine D4 receptor antagonist-1；2-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-1H-benzimidazole
• 化学式: C₁₈H₁₉ClN₄
• 分子量: 326.829
• InChiKey: BRLVOVGBNYPHBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯甲基苯并咪唑 、 1-(3-氯苯基)哌嗪 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 生成 2-[4-(3-Chloro-phenyl)-piperazin-1-ylmethyl]-1H-benzoimidazole
  参考文献：
  名称：

  Dopamine D₄ Ligands and Models of Receptor Activation:  2-(4-Pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole and Related Heteroarylmethylarylpiperazines Exhibit a Substituent Effect Responsible for Additional Efficacy Tuning

  摘要：

  A series of subtype selective dopamine D-4 receptor ligands from the hetroarylmethylphenylpiperazine class have been discovered that exhibit a remarkable structure-activity relationship (SAR), revealing a substituent effect in which regiosubstitution on the terminal arylpiperazine ring can modulate functional or intrinsic activity. Other structure-dependent efficacy studies in the dopamine D-4 field have suggested a critical interaction of the heteroarylmethyl moiety with specific protein microdomains in controlling intrinsic activity. Our studies indicate that for some binding orientations, the phenylpiperazine moiety also plays a key role in determining efficacy. These data also implicate a kinetic or efficiency term, contained within measured functional affinities for agonists, which support a sequential binding and conformational stabilization model for receptor activation. The structural similarity between partial agonist and antagonist, within this subset of ligands, and lack of bioisosterisin for this substituent effect are key phenomena for these hypotheses.

  DOI：

  10.1021/jm0305669