Ethyl 1-ethyl-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate | 720705-54-4

• 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: Ethyl 1-ethyl-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
• 英文别名: ethyl 1-ethyl-4-[methyl(oxan-4-yl)amino]pyrazolo[3,4-b]pyridine-5-carboxylate
• CAS: 720705-54-4
• 化学式: C₁₇H₂₄N₄O₃
• 分子量: 332.403
• InChiKey: JXEBIPKDQUARND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  sodium hydroxide 、 Ethyl 1-ethyl-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 在 水 、 盐酸 、 二氯甲烷 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以to give Intermediate 52 as a white solid (0.65 g)的产率得到1-Ethyl-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid
  参考文献：
  名称：

  Pyrazolo[3,4-B]pyridine compounds, and their use as phosphodiesterase inhibitors

  摘要：

  本发明涉及式（I）化合物或其盐：其中：R1是C1-4烷基，C1-3氟代烷基或—（CH2）2OH; R2是氢原子（H），甲基或C1氟代烷基; R3a是氢原子（H）或C1-3烷基; R3是可选的取代的支链C3-6烷基，可选的取代的C3-8环烷基，可选的取代的单不饱和C5-7环烯基，可选的取代的苯基，或亚式（aa），（bb）或（cc）的可选取代的杂环基：其中n1和n2独立地为1或2; Y为O，S，SO2或NR4; Het为亚式（i），（ii），（iii），（iv）或（v）：所述化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。还提供了使用式（I）的化合物或其药学上可接受的盐制备药物，用于治疗和/或预防哺乳动物（例如人类）的炎症和/或过敏性疾病，例如慢性阻塞性肺疾病（COPD），哮喘或过敏性鼻炎。

  公开号：

  US07528148B2
• 作为产物：
  描述：

  N-甲基四氢-2H-吡喃-4-胺 、 4-氯-1-乙基-1H-吡唑[3,4-b]吡啶-5-羧酸乙酯 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 Ethyl 1-ethyl-4-[methyl(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
  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

• Pyrazolo [3,4-b] pyridine compounds, and their use as phosphodiesterase inhibitors
  申请人：Allen George David

  公开号：US20060252790A1

  公开（公告）日：2006-11-09

  The invention relates to a compound of formula (I) or a salt thereof: wherein: R 1 is C 1-4 alkyl, C 1-3 fluoroalkyl or —(CH 2 ) 2 OH; R 2 is a hydrogen atom (H), methyl or C 1 fluoroalkyl; R 3a is a hydrogen atom (H) or C 1-3 alkyl; R 3 is optionally substituted branched C 3-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted mono-unsaturated-C 5-7 cycloalkenyl, optionally substituted phenyl, or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc): in which n 1 and n 2 independently are 1 or 2; and Y is O, S, SO 2 , or NR 4 ; and wherein Het is of sub-formula (i), (ii), (iii), (iv) or (v): The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.

  本发明涉及式（I）化合物或其盐： 其中：R1是C1-4烷基，C1-3氟代烷基或—（CH2）2OH；R2是氢原子（H），甲基或C1氟代烷基；R3a是氢原子（H）或C1-3烷基；R3是可选的取代的支链C3-6烷基，可选的取代的C3-8环烷基，可选的取代的单不饱和C5-7环烯基，可选的取代的苯基，或者是亚式（aa），（bb）或（cc）的可选取代的杂环基： 其中n1和n2独立地为1或2；Y是O，S，SO2或NR4；而Het是亚式（i），（ii），（iii），（iv）或（v）： 这些化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。还提供了使用式（I）化合物或其药学上可接受的盐制造药物，用于治疗和/或预防哺乳动物（例如人类）的炎症和/或过敏性疾病，例如慢性阻塞性肺疾病（COPD），哮喘或过敏性鼻炎。
• PYRAZOLO¬3,4-B PYRIDINE COMPOUNDS, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1581532B1

  公开（公告）日：2010-04-28
• US7528148B2
  申请人：——

  公开号：US7528148B2

  公开（公告）日：2009-05-05
• [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：WO2004056823A1

  公开（公告）日：2004-07-08

  The invention relates to a compound of formula (I) or a salt thereof: Formula (I) wherein: R1 is C1-4alkyl, C1-3fluoroalkyl or -(CH2)2OH; R2 is a hydrogen atom (H), methyl or C1fluoroalkyl; R3a is a hydrogen atom (H) or C1-3alkyl; R3 is optionally substituted branched C3-6alkyl, optionally substituted C3-8cycloalkyl, optionally substituted mono-unsaturated-C5-7cycloalkenyl, optionally substituted phenyl, or an optionally substituted heterocyclic group of sub-formula (aa), or (bb) or (cc) in which n1 and n2 independently are 1 or 2; and Y is O, S, SO2, or NR4; and wherein Het is of sub-formula (i), or (ii), or (iii), or (iv) or (v). The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.
• Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors
  作者：J. Nicole Hamblin、Tony D.R. Angell、Stuart P. Ballantine、Caroline M. Cook、Anthony W.J. Cooper、John Dawson、Christopher J. Delves、Paul S. Jones、Mika Lindvall、Fiona S. Lucas、Charlotte J. Mitchell、Margarete Y. Neu、Lisa E. Ranshaw、Yemisi E. Solanke、Don O. Somers、Joanne O. Wiseman

  DOI：10.1016/j.bmcl.2008.05.052

  日期：2008.7

  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.