sodium 5-{[4-({[(5-bromo-1H-indazol-3-yl)carbonyl]amino}-methyl)piperidin-1-yl]methyl}furan-2-carboxylate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: sodium 5-{[4-({[(5-bromo-1H-indazol-3-yl)carbonyl]amino}-methyl)piperidin-1-yl]methyl}furan-2-carboxylate
• 英文别名: sodium;5-[[4-[[(5-bromo-1H-indazole-3-carbonyl)amino]methyl]piperidin-1-yl]methyl]furan-2-carboxylate
• 化学式: C₂₀H₂₀BrN₄O₄*Na
• 分子量: 483.297
• InChiKey: BJZXFSYKVIJXEL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.07
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  sodium 5-{[4-({[(5-bromo-1H-indazol-3-yl)carbonyl]amino}-methyl)piperidin-1-yl]methyl}furan-2-carboxylate 、 4-甲氧基吡啶-3-硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以24%的产率得到5-({4-[({[5-(4-methoxypyridin-3-yl)-1H-indazol-3-yl]carbonyl}amino)methyl]piperidin-1-yl}methyl)furan-2-carboxylic acid
  参考文献：
  名称：

  Hit Optimization of 5-Substituted-N-(piperidin-4-ylmethyl)-1H-indazole-3-carboxamides: Potent Glycogen Synthase Kinase-3 (GSK-3) Inhibitors with in Vivo Activity in Model of Mood Disorders

  摘要：

  Novel treatments for bipolar disorder with improved efficacy and broader spectrum of activity are urgently needed. Glycogen synthase kinase 3 beta (GSK-3 beta) has been suggested to be a key player in the pathophysiology of bipolar disorder. A series of novel GSK-3 beta inhibitors having the common N-[(1-alkylpiperidin-4-yl)methyl]-1H-indazole-3-carboxamide scaffold were prepared taking advantage of an X-ray cocrystal structure of compound 5 with GSK-3 beta. We probed different substitutions at the indazole 5-position and at the piperidine-nitrogen to obtain potent ATP-competitive GSK-3 beta inhibitors with good cell activity. Among the compounds assessed in the in vivo PK experiments, 14i showed, after i.p. dosing, encouraging plasma PK profile and brain exposure, as well as efficacy in a mouse model of mania. Compound 14i was selected for further in vitro/in vivo pharmacological evaluation, in order to elucidate the use of ATP-competitive GSK-3 beta inhibitors as new tools in the development of new treatments for mood disorders

  DOI：

  10.1021/acs.jmedchem.5b01208
• 作为产物：
  描述：

  ethyl 5-{[4-({[(5-bromo-1H-indazol-3-yl)carbonyl]amino}methyl)-piperidin-1-yl]methyl}furan-2-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以98%的产率得到sodium 5-{[4-({[(5-bromo-1H-indazol-3-yl)carbonyl]amino}-methyl)piperidin-1-yl]methyl}furan-2-carboxylate
  参考文献：
  名称：

  Hit Optimization of 5-Substituted-N-(piperidin-4-ylmethyl)-1H-indazole-3-carboxamides: Potent Glycogen Synthase Kinase-3 (GSK-3) Inhibitors with in Vivo Activity in Model of Mood Disorders

  摘要：

  Novel treatments for bipolar disorder with improved efficacy and broader spectrum of activity are urgently needed. Glycogen synthase kinase 3 beta (GSK-3 beta) has been suggested to be a key player in the pathophysiology of bipolar disorder. A series of novel GSK-3 beta inhibitors having the common N-[(1-alkylpiperidin-4-yl)methyl]-1H-indazole-3-carboxamide scaffold were prepared taking advantage of an X-ray cocrystal structure of compound 5 with GSK-3 beta. We probed different substitutions at the indazole 5-position and at the piperidine-nitrogen to obtain potent ATP-competitive GSK-3 beta inhibitors with good cell activity. Among the compounds assessed in the in vivo PK experiments, 14i showed, after i.p. dosing, encouraging plasma PK profile and brain exposure, as well as efficacy in a mouse model of mania. Compound 14i was selected for further in vitro/in vivo pharmacological evaluation, in order to elucidate the use of ATP-competitive GSK-3 beta inhibitors as new tools in the development of new treatments for mood disorders

  DOI：

  10.1021/acs.jmedchem.5b01208