2-(2-phenylpiperidin-1-yl)-1H-benzoimidazole | 1086420-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(2-phenylpiperidin-1-yl)-1H-benzoimidazole
• 英文别名: 2-(2-phenylpiperidin-1-yl)-1H-benzimidazole
• CAS: 1086420-42-9
• 化学式: C₁₈H₁₉N₃
• 分子量: 277.369
• InChiKey: SWDBIAFYVWQAFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  31.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氯苯并咪唑 、 2-苯基哌啶 以 乙腈 为溶剂， 以10%的产率得到2-(2-phenylpiperidin-1-yl)-1H-benzoimidazole
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies of 2-(N-Substituted)-aminobenzimidazoles as Potent Negative Gating Modulators of Small Conductance Ca²⁺-Activated K⁺ Channels

  摘要：

  Small conductance Ca2+-activated K+ channels (SK channels) participate in the control of neuronal excitability, in the shaping of action potential firing patterns, and in the regulation of synaptic transmission. SK channel inhibitors have the potential of becoming new drugs for treatment of various psychiatric and neurological diseases such as depression, cognition impairment, and Parkinson's disease. In the present study we describe the structure-activity relationship (SAR) of a class of 2-(N-substituted)-2-aminobenzimidazoles that constitute a novel class of selective SK channel inhibitors that, in contrast to classical SK inhibitors, do not block the pore of the channel. The pore blocker apamin is not displaced by these compounds in binding studies, and they still inhibit SK channels in which the apamin binding site has been abolished by point mutations. These novel SK inhibitors shift the concentration-response curve for Ca2+ toward higher values and represent the first example of negative gating modulation as a mode-of-action for inhibition of SK channels. The first described compound in this class is NS8593 (14), and the most potent analogue identified in this study is the racemic compound 39 (NS11757), which reversibly inhibits SK3-rnediated currents with a K-d value of 9 nM.

  DOI：

  10.1021/jm800809f

文献信息

• Synthesis and Structure−Activity Relationship Studies of 2-(N-Substituted)-aminobenzimidazoles as Potent Negative Gating Modulators of Small Conductance Ca²⁺-Activated K⁺ Channels
  作者：Ulrik S. Sørensen、Dorte Strøbæk、Palle Christophersen、Charlotte Hougaard、Marianne L. Jensen、Elsebet Ø. Nielsen、Dan Peters、Lene Teuber

  DOI：10.1021/jm800809f

  日期：2008.12.11

  Small conductance Ca2+-activated K+ channels (SK channels) participate in the control of neuronal excitability, in the shaping of action potential firing patterns, and in the regulation of synaptic transmission. SK channel inhibitors have the potential of becoming new drugs for treatment of various psychiatric and neurological diseases such as depression, cognition impairment, and Parkinson's disease. In the present study we describe the structure-activity relationship (SAR) of a class of 2-(N-substituted)-2-aminobenzimidazoles that constitute a novel class of selective SK channel inhibitors that, in contrast to classical SK inhibitors, do not block the pore of the channel. The pore blocker apamin is not displaced by these compounds in binding studies, and they still inhibit SK channels in which the apamin binding site has been abolished by point mutations. These novel SK inhibitors shift the concentration-response curve for Ca2+ toward higher values and represent the first example of negative gating modulation as a mode-of-action for inhibition of SK channels. The first described compound in this class is NS8593 (14), and the most potent analogue identified in this study is the racemic compound 39 (NS11757), which reversibly inhibits SK3-rnediated currents with a K-d value of 9 nM.