5-bromo-N-{[1-(2-methoxyethyl)piperidin-4-yl]methyl}-1H-indazole-3-carboxamide | 1452582-32-9

• 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: 5-bromo-N-{[1-(2-methoxyethyl)piperidin-4-yl]methyl}-1H-indazole-3-carboxamide
• 英文别名: 5-bromo-N-{[1-(2-methoxyethyl)piperidine-4-yl]methyl}-1H-indazole-3-carboxamide；5-bromo-N-[[1-(2-methoxyethyl)piperidin-4-yl]methyl]-1H-indazole-3-carboxamide
• CAS: 1452582-32-9
• 化学式: C₁₇H₂₃BrN₄O₂
• 分子量: 395.299
• InChiKey: AWDQJULXXOYTNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-N-{[1-(2-methoxyethyl)piperidin-4-yl]methyl}-1H-indazole-3-carboxamide 、 2-甲基-5-吡啶硼酸 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18%的产率得到N-{[1-(2-methoxyethyl)piperidin-4-yl]methyl}-5-(6-methylpyridin-3-yl)-1H-indazole-3-carboxamide
  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：

  5-溴吲唑-3-甲酸 、 1-[1-(2-甲氧基乙基)哌啶-4-基]甲胺 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以9.5 g的产率得到5-bromo-N-{[1-(2-methoxyethyl)piperidin-4-yl]methyl}-1H-indazole-3-carboxamide
  参考文献：
  名称：

  [EN] 1H-INDAZOLE-3-CARBOXAMIDE COMPOUNDS AS GLYCOGEN SYNTHASE KINASE 3 BETA INHIBITORS
  [FR] COMPOSÉS 1H-INDAZOLE-3-CARBOXAMIDE EN TANT QU'INHIBITEURS DE LA GLYCOGÈNE SYNTHASE KINASE 3 BÊTA

  摘要：

  本发明涉及具有以下一般式（I）的1H-吲唑-3-羧酰胺化合物作为糖原合成酶激酶3β（GSK-3ß）抑制剂，并且涉及它们在治疗GSK-3β相关疾病中的用途，例如（i）胰岛素抵抗性疾病；（ii）神经退行性疾病；（iii）情绪障碍；（iv）精神分裂症障碍；（v）癌症性疾病；（vi）炎症；（vii）物质滥用障碍；（viii）癫痫病；和（ix）神经病性疼痛。

  公开号：

  WO2013124158A1

文献信息

• 1H-INDAZOLE-3-CARBOXAMIDE COMPOUNDS AS GLYCOGEN SYNTHASE KINASE 3 BETA INHIBITORS
  申请人：AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A.

  公开号：US20150057294A1

  公开（公告）日：2015-02-26

  The present invention relates to the 1H-indazole-3-carboxamide compounds having the following general formula (I) as glycogen synthase kinase 3 beta (GSK-3β) inhibitors and to their use in the treatment of GSK-3p-related disorders such as, for example, (i) insulin-resistance disorders; (ii) neurodegenerative diseases; (iii) mood disorders; (iv) schizophrenic disorders; (v) cancerous disorders; (vi) inflammation, (vii) substance abuse disorders; (viii) epilepsies; and (ix) neuropathic pain.

  本发明涉及具有以下一般式（I）的1H-吲唑-3-羧酰胺化合物作为糖原合成酶激酶3β（GSK-3β）抑制剂，并且涉及它们在治疗GSK-3β相关疾病中的应用，例如（i）胰岛素抵抗性疾病；（ii）神经退行性疾病；（iii）情绪障碍；（iv）精神分裂症；（v）癌症性疾病；（vi）炎症；（vii）物质滥用障碍；（viii）癫痫；和（ix）神经病理性疼痛。
• 1H-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
  申请人：AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A.

  公开号：US10160746B2

  公开（公告）日：2018-12-25

  The present invention relates to the 1H-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta (GSK-3β) inhibitors and to their use in the treatment of GSK-3β-related disorders such as, for example, (i) insulin-resistance disorders; (ii) neurodegenerative diseases; (iii) mood disorders; (iv) schizophrenic disorders; (v) cancerous disorders; (vi) inflammation, (vii) substance abuse disorders; (viii) epilepsies; and (ix) neuropathic pain.

  本发明涉及作为糖原合酶激酶3β（GSK-3β）抑制剂的1H-吲唑-3-甲酰胺化合物，以及它们在治疗GSK-3β相关疾病中的用途，例如，(i) 胰岛素抵抗性疾病；(ii) 神经退行性疾病；(iii) 情绪障碍；(iv) 精神分裂症；(v) 癌症；(vi) 炎症；(vii) 药物滥用障碍；(viii) 癫痫；以及 (ix) 神经性疼痛。
• US9611249B2
  申请人：——

  公开号：US9611249B2

  公开（公告）日：2017-04-04