4-amino-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester | 34963-96-7

• 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: 4-amino-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester
• 英文别名: Ethyl 4-amino-1-ethylpyrazolo[3,4-b]pyridine-5-carboxylate
• CAS: 34963-96-7
• 化学式: C₁₁H₁₄N₄O₂
• 分子量: 234.258
• InChiKey: DFRDNITYOZQPHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 4-amino-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 16.0h， 生成 Ethyl 4-benzamido-1-ethylpyrazolo[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
• 作为产物：
  描述：

  在 水 作用下， 反应 2.0h， 生成 4-amino-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester
  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 PDE4 INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1940835B1

  公开（公告）日：2011-03-30
• [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：WO2004024728A2

  公开（公告）日：2004-03-25

  The invention relates to a compound of formula (I) or a salt thereof: wherein:R1 is C1-4alkyl, C1-3fluoroalkyl, -CH2CH2OH or -CH2CH2CO2C1-2alkyl;R2 is a hydrogen atom (H), methyl or C1fluoroalkyl;R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee): ; and wherein X is NR4R5 or OR5a. 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.
• [EN] PYRAZOLO [3,4-B] PYRIDINE COMPOUNDS, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] COMPOSES PYRAZOLO [3,4-B] PYRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA PHOSPHODIESTERASE
  申请人：GLAXO GROUP LTD

  公开号：WO2005058892A1

  公开（公告）日：2005-06-30

  The invention provides a compound of formula (I) or a salt thereof, wherein Ar has the sub-formula (x) or (z) and wherein R3 is optionally substituted C3-8cycloalkyl, optionally substituted C5-7 cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc), or a bicyclic group (ee); and wherein R4 is H, C1-3 alkyl, C1-2fluoroalkyl, cyclopropyl, CH2OR4a, CH(Me)OR4a, or CH2CH2OR4a; and R5 is inter alia H, C1-8alkyl, C1-8fluoroalkyl, C3-8 cycloalkyl, certain substituted alkyl groups, -(CH2)n13- Het, or optionally substituted phenyl or CH2-Ph; or R4 and R5 taken together are -(CH2)p1- or (CH2)p3 X5 (CH2)p4- ; provided that at least one of R4 and R5 is not a hydrogen atom (H). The invention also provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis.
• [EN] PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLO[3,4-B]PYRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2008015437A1

  公开（公告）日：2008-02-07

  [EN] The invention provides a compound of formula (I) or a salt thereof: wherein Ar has the sub-formula (w), (y), (z1) or (z2): and wherein: Q¹ is NH or NMe, in which case Q² is -C(O)-, -S(O)₂-, -C(O)NH- or -C(O)NMe-; or Q¹ is a bond or -0-, in which case Q² is a bond; or Q¹ is -C(O)-, in which case Q² is NH or NMe; or Q¹ is -S(O)₂-, in which case Q² is NH, NMe or a bond; and Q³ is a bond, NH or NMe; and L is (CH₂)_n wherein n is 4 to 13; or L is -(CH₂)_m
  [FR] L'invention concerne un composé représenté par la formule (I) ou un sel de celui-ci. Dans ladite formule (I), Ar est représenté par la sous-formule (w), (y), (z1) ou (z2), où Q¹ représente NH ou NMe, auquel cas Q² représente -C(O)-, -S(O)₂-, -C(O)NH- ou -C(O)NMe-; ou Q¹ représente une liaison ou -0-, auquel cas Q² représente une liaison; ou Q¹ représente -C(O)-, auquel cas Q² représente NH ou NMe; ou Q¹ représente -S(O)₂-, auquel cas Q² représente NH, NMe ou une liaison; et Q³ représente une liaison, NH ou NMe; et L représente (CH₂)_n, n étant compris entre 4 et 13; ou L représente -(CH₂)_m