1-乙基-4-((四氢-2H-吡喃-4-基)氨基)-1H-吡唑并[3,4-b]吡啶-5-碳酰肼 | 730937-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 中文名称: 1-乙基-4-((四氢-2H-吡喃-4-基)氨基)-1H-吡唑并[3,4-b]吡啶-5-碳酰肼
• 英文名称: 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carbohydrazide
• 英文别名: 1-ethyl-4-[(tetrahydro-2H-pyran-4-yl)amino]-1H-Pyrazolo[3,4-b]pyridine-5-carboxylic acid hydrazide；1-ethyl-4-(oxan-4-ylamino)pyrazolo[3,4-b]pyridine-5-carbohydrazide
• CAS: 730937-45-8
• 化学式: C₁₄H₂₀N₆O₂
• 分子量: 304.352
• InChiKey: KOPOGYKTDYQRII-UHFFFAOYSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-乙基-4-((四氢-2H-吡喃-4-基)氨基)-1H-吡唑并[3,4-b]吡啶-5-碳酰肼 、 N-乙酰甘氨酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-[2-(2-{[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}hydrazinyl)-2-oxoethyl]ethanamide
  参考文献：
  名称：

  Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

  摘要：

  Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett. 2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-alpha production from isolated human peripheral blood mononuclear cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.136
• 作为产物：
  描述：

  Tert-butyl 2-{[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}hydrazinecarboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以100%的产率得到1-乙基-4-((四氢-2H-吡喃-4-基)氨基)-1H-吡唑并[3,4-b]吡啶-5-碳酰肼
  参考文献：
  名称：

  Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

  摘要：

  Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett. 2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-alpha production from isolated human peripheral blood mononuclear cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.136

文献信息

• US7528148B2
  申请人：——

  公开号：US7528148B2

  公开（公告）日：2009-05-05
• [EN] TREATMENT OF ANXIETY DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES DE L'ANXIÉTÉ
  申请人：GLAXO GROUP LTD

  公开号：WO2011107394A1

  公开（公告）日：2011-09-09

  Use of a compound of formula (I): 5-5-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]- 1,3,4-oxadiazol-2-yl} -1-ethyl-N-(tetrahydro-2H-pyran-4-yl)- 1H-pyrazolo[3,4-b]pyridin-4-amine, Formula (I), or a pharmaceutically acceptable salt thereof for the treatment of anxiety disorders and a process for its preparation.