tert-butyl (5-(1-(4-methylbenzyl)-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methylcarbamate | 1151513-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl (5-(1-(4-methylbenzyl)-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methylcarbamate
• 英文别名: tert-butyl N-[[5-[1-[(4-methylphenyl)methyl]indazol-3-yl]-1,2,4-oxadiazol-3-yl]methyl]carbamate
• CAS: 1151513-05-1
• 化学式: C₂₃H₂₅N₅O₃
• 分子量: 419.483
• InChiKey: YJZCMXYATVRJRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-(1-(4-methylbenzyl)-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methylcarbamate 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 18.0h， 以99%的产率得到(5-(1-(4-methylbenzyl)-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methanamine
  参考文献：
  名称：

  Oxadiazolylindazole Sodium Channel Modulators are Neuroprotective toward Hippocampal Neurones

  摘要：

  We report the discovery of a new class of neuroprotective voltage-dependent sodium channel modulators exemplified by (5-(1-benzyl-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methanamine. 11 (CFM1178). The compounds were inhibitors of [C-14]guanidinium ion flux in rat forebrain synaptosomes and displaced binding of the sodium channel ligand [H-3]BW202W92. 11 and the corresponding N-2-benzyl isomer, 38 (CFM6058), demonstrated neuroprotective activity in hippocampal slices comparable to sipatrigine. CYP450 enzyme inhibition observed with 11 was reduced with 38. In electrophysiological experiments on dissociated hippocampal neurons, these two compounds caused use- and voltage-dependent block of sodium currents. Sodium channel isoform profiling against Na(v)1.1-1.8 demonstrated that the standard sodium channel blocker lamotrigine had modest activity against Na(v)1.1, while sipatrigine was generally more potent and less selective. 11 and 38 showed potent activity against Na(v)1.6, pointing to pharmacological block of this isoform being consistent with the neuroprotective effect. 38 also showed use dependent block of Na(v)1.6 in HEK cells.

  DOI：

  10.1021/jm801180p
• 作为产物：
  描述：

  3-[3-tert-butoxycarbonylaminomethyl-1,2,4-oxadiazol-5-yl]indazole 、 alkaline earth salt of/the/ methylsulfuric acid 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以42%的产率得到tert-butyl (5-(1-(4-methylbenzyl)-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methylcarbamate
  参考文献：
  名称：

  Oxadiazolylindazole Sodium Channel Modulators are Neuroprotective toward Hippocampal Neurones

  摘要：

  We report the discovery of a new class of neuroprotective voltage-dependent sodium channel modulators exemplified by (5-(1-benzyl-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methanamine. 11 (CFM1178). The compounds were inhibitors of [C-14]guanidinium ion flux in rat forebrain synaptosomes and displaced binding of the sodium channel ligand [H-3]BW202W92. 11 and the corresponding N-2-benzyl isomer, 38 (CFM6058), demonstrated neuroprotective activity in hippocampal slices comparable to sipatrigine. CYP450 enzyme inhibition observed with 11 was reduced with 38. In electrophysiological experiments on dissociated hippocampal neurons, these two compounds caused use- and voltage-dependent block of sodium currents. Sodium channel isoform profiling against Na(v)1.1-1.8 demonstrated that the standard sodium channel blocker lamotrigine had modest activity against Na(v)1.1, while sipatrigine was generally more potent and less selective. 11 and 38 showed potent activity against Na(v)1.6, pointing to pharmacological block of this isoform being consistent with the neuroprotective effect. 38 also showed use dependent block of Na(v)1.6 in HEK cells.

  DOI：

  10.1021/jm801180p

文献信息

• Oxadiazolylindazole Sodium Channel Modulators are Neuroprotective toward Hippocampal Neurones
  作者：Lisa A. Clutterbuck、Cristina Garcia Posada、Cristina Visintin、Dieter R. Riddall、Barrie Lancaster、Paul J. Gane、John Garthwaite、David L. Selwood

  DOI：10.1021/jm801180p

  日期：2009.5.14

  We report the discovery of a new class of neuroprotective voltage-dependent sodium channel modulators exemplified by (5-(1-benzyl-1H-indazol-3-yl)-1,2,4-oxadiazol-3-yl)methanamine. 11 (CFM1178). The compounds were inhibitors of [C-14]guanidinium ion flux in rat forebrain synaptosomes and displaced binding of the sodium channel ligand [H-3]BW202W92. 11 and the corresponding N-2-benzyl isomer, 38 (CFM6058), demonstrated neuroprotective activity in hippocampal slices comparable to sipatrigine. CYP450 enzyme inhibition observed with 11 was reduced with 38. In electrophysiological experiments on dissociated hippocampal neurons, these two compounds caused use- and voltage-dependent block of sodium currents. Sodium channel isoform profiling against Na(v)1.1-1.8 demonstrated that the standard sodium channel blocker lamotrigine had modest activity against Na(v)1.1, while sipatrigine was generally more potent and less selective. 11 and 38 showed potent activity against Na(v)1.6, pointing to pharmacological block of this isoform being consistent with the neuroprotective effect. 38 also showed use dependent block of Na(v)1.6 in HEK cells.