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.
• Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR
  作者：Charlotte J. Mitchell、Stuart P. Ballantine、Diane M. Coe、Caroline M. Cook、Christopher J. Delves、Mike D. Dowle、Chris D. Edlin、J. Nicole Hamblin、Stuart Holman、Martin R. Johnson、Paul S. Jones、Sue E. Keeling、Michael Kranz、Mika Lindvall、Fiona S. Lucas、Margarete Neu、Yemisi E. Solanke、Don O. Somers、Naimisha A. Trivedi、Joanne O. Wiseman

  DOI：10.1016/j.bmcl.2010.07.136

  日期：2010.10

  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.