1-ethyl-5-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine | 720704-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-ethyl-5-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine
• CAS: 720704-21-2
• 化学式: C₂₁H₂₁FN₆O₂
• 分子量: 408.435
• InChiKey: ZENDFWOFRUOXDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 1-ethyl-5-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine
  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

• 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