1-ethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridine-5-carbonyl chloride | 1253583-68-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 1-ethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridine-5-carbonyl chloride
• CAS: 1253583-68-4
• 化学式: C₁₄H₁₇ClN₄O₂
• 分子量: 308.768
• InChiKey: JFTYWXLOTMICHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.04
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-ethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridine-5-carbonyl chloride 在 氨 作用下， 反应 0.5h， 生成 N-benzyl-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
  参考文献：
  名称：

  Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors

  摘要：

  Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to be a potent and selective PDE4 inhibitor which also inhibits LPS induced TNF-alpha production from isolated human peripheral blood mononuclear cells and has an encouraging rat PK profile suitable for oral dosing.

  DOI：

  10.1016/j.bmcl.2008.05.052
• 作为产物：
  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-羧酸 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 1.0h， 生成 1-ethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridine-5-carbonyl chloride
  参考文献：
  名称：

  Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors

  摘要：

  Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to be a potent and selective PDE4 inhibitor which also inhibits LPS induced TNF-alpha production from isolated human peripheral blood mononuclear cells and has an encouraging rat PK profile suitable for oral dosing.

  DOI：

  10.1016/j.bmcl.2008.05.052

文献信息

• 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.
• [EN] PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] COMPOSES DE PYRAZOLO[3,4-B]PYRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PHOSPHODIESTERASE
  申请人：GLAXO GROUP LTD

  公开号：WO2004024728A3

  公开（公告）日：2004-10-21