4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid | 675112-65-9

• 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-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid
• 英文别名: 4-cyclohexylamino-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid；4-(cyclohexylamino)-1-ethylpyrazolo[3,4-b]pyridine-5-carboxylic acid
• CAS: 675112-65-9
• 化学式: C₁₅H₂₀N₄O₂
• 分子量: 288.349
• InChiKey: NZPHRHYVEFSWFF-UHFFFAOYSA-N

物化性质

• 沸点：
  512.9±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成
  参考文献：
  名称：

  Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer’s disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids

  摘要：

  A series of tacrine-pyrazolo [3,4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer's disease (AD). Compound 10j, which is tacrine linked with pyrazolo[3,4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125 mu M. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50, value of 0.449 and 0.271 mu M, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD.

  DOI：

  10.1016/j.bmcl.2019.06.056
• 作为产物：
  描述：

  5-氨基-1-乙基吡唑 在 乙醇 、 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 反应 44.0h， 生成 4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid
  参考文献：
  名称：

  Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer’s disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids

  摘要：

  A series of tacrine-pyrazolo [3,4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer's disease (AD). Compound 10j, which is tacrine linked with pyrazolo[3,4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125 mu M. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50, value of 0.449 and 0.271 mu M, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD.

  DOI：

  10.1016/j.bmcl.2019.06.056

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：US20060089375A1

  公开（公告）日：2006-04-27

  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, —CH 2 CH 2 OH or —CH 2 CH 2 CO 2 C 1-2 alkyl; R 2 is a hydrogen atom (H), methyl or C 1 fluoroalkyl; R 3 is optionally substituted C 3-8 cycloalkyl or optionally substituted mono-unsaturated-C 5-7 cycloalkenyl 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 in which Y is O, S, SO 2 , or NR 10 ; or R 3 is a bicyclic group (dd) or (ee): and wherein X is NR 4 R 5 or OR 5a . 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.

  本发明涉及一种化合物或其盐，其化学式为（I）：其中：R1为C1-4烷基，C1-3氟烷基，-CH2CH2OH或-CH2CH2CO2C1-2烷基；R2为氢原子（H），甲基或C1氟烷基；R3为可选取代的C3-8环烷基或可选取代的单不饱和C5-7环烯基或亚式（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；且其中Y为O，S，SO2或NR10；或者R3为双环基（dd）或（ee）：其中X为NR4R5或OR5a。该化合物为磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。本发明还提供了使用化合物（I）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：Allen George David

  公开号：US20070111995A1

  公开（公告）日：2007-05-17

  The invention provides pyrazolo[3,4-b]pyridine compounds of formula (I) having a —C(O)—NH—C(R 4 )(R 5 )-aryl substituent at the 5-position of the pyrazolo[3,4-b]pyridine ring system wherein at least one of R 4 and R 5 is not a hydrogen atom (H) compound or a salt thereof: wherein Ar has the sub-formula (x) or (z). These compounds are useful as inhibitors of PDE4.

  本发明提供了式(I)的吡唑并[3,4-b]吡啶化合物，其在吡唑并[3,4-b]吡啶环系的5位具有—C(O)—NH—C(R4)(R5)-芳基取代基，其中R4和R5中至少有一个不是氢原子（H）化合物或其盐：其中Ar具有亚式（x）或（z）。这些化合物可用作PDE4的抑制剂。
• PYRAZOLO [3,4-B] PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS
  申请人：Allen David George

  公开号：US20080132536A1

  公开（公告）日：2008-06-05

  The invention provides a compound of formula (I) or a salt thereof: wherein Ar has the sub-formula (x) or (z): and wherein R 3 is optionally substituted C 3-8 cycloalkyl, optionally substituted C 5-7 cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc), or a bicyclic group (ee); and wherein R 4 is H, C 1-3 alkyl, C 1-2 fluoroalkyl, cyclopropyl, —CH 2 OR 4a , —CH(Me)OR 4a , or —CH 2 CH 2 OR 4a ; and R 5 is inter alia H, C 1-8 alkyl, C 1-3 fluoroalkyl, C 3-8 cycloalkyl, certain substituted alkyl groups, —(CH 2 ) n 13 -Het, or optionally substituted phenyl or —CH 2 -Ph; or R 4 and R 5 taken together are —(CH 2 ) p 1 — or —(CH 2 ) p 3 —X 5 —(CH 2 ) p 4 —; provided that at least one of R 4 and R 5 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.

  该发明提供了式(I)的化合物或其盐： 其中Ar具有亚式(x)或(z)： 其中，R3是可选的取代C3-8环烷基，可选的取代C5-7环烯基，可选的取代的杂环基(aa)，(bb)或(cc)，或者是双环基(ee)； 其中，R4是氢，C1-3烷基，C1-2氟代烷基，环丙基，—CH2OR4a，—CH(Me)OR4a或—CH2CH2OR4a； 而R5则是包括氢、C1-8烷基、C1-3氟代烷基、C3-8环烷基、某些取代烷基、—(CH2)n13-Het，或可选取代的苯基或—CH2-Ph等的基团； 或者，R4和R5在一起是—(CH2)p1—或—(CH2)p3—X5—(CH2)p4—； 但是至少其中一个R4和R5不是氢原子（H）。 该发明还提供了将这些化合物用作磷酸二酯酶IV（PDE4）的抑制剂和/或用于治疗和/或预防炎症和/或过敏性疾病，如慢性阻塞性肺疾病（COPD）、哮喘、类风湿性关节炎、过敏性鼻炎或特应性皮炎的用途。
• Pyrazolo[3,4-b]Pyridine Compounds, and their Use as Phosphodiesterase Inhibitors
  申请人：ALLEN David George

  公开号：US20080175914A1

  公开（公告）日：2008-07-24

  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, —CH 2 CH 2 OH or —CH 2 CH 2 CO 2 C 1-2 alkyl; R 2 is a hydrogen atom (H), methyl or C 1 fluoroalkyl; R 3 is optionally substituted C 3-8 cycloalkyl or optionally substituted mono-unsaturated-C 5-7 cycloalkenyl 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 in which Y is O, S, SO 2 , or NR 10 ; or R 3 is a bicyclic group (dd) or (ee): and wherein X is NR 4 R 5 or OR 5a . The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE 4 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.

  本发明涉及公式（I）的化合物或其盐： 其中： R1是C1-4烷基，C1-3氟烷基，-CH2CH2OH或-CH2CH2CO2C1-2烷基; R2是氢原子（H），甲基或C1氟烷基; R3是可选取代的C3-8环烷基或可选取代的单不饱和C5-7环烯基或亚公式（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NR10; 或R3是双环基（dd）或（ee）： 其中X是NR4R5或OR5a。 该化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。本发明还提供了公式（I）的化合物或其药学上可接受的盐的用途，用于制造治疗和/或预防哺乳动物，如人类的炎症性和/或过敏性疾病的药物，例如慢性阻塞性肺疾病（COPD），哮喘或过敏性鼻炎。
• PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
  申请人：Rudra Sonali

  公开号：US20110130403A1

  公开（公告）日：2011-06-02

  The present invention relates to phosphodiesterase (PDE) type 4, phosphodiesterase (PDE) type 7 and dual PDE type 4/PDE type 7 inhibitors. Compounds disclosed hereinf having the structure of Formula I: can be useful in the treatment, prevention, inhibition or suppression of CNS diseases, for example, multiple sclerosis; various pathological conditions such as diseases affecting the immune system, including AIDS, rejection of transplant, auto-immune disorders such as T-cell related diseases, for example, rheumatoid arthritis; inflammatory diseases such as respiratory inflammation diseases including chronic obstructive pulmonary disease (COPD), asthma, bronchitis, allergic rhinitis, adult respiratory distress syndrome (ARDS) and other inflammatory diseases including but not limited to psoriasis, shock, atopic dermatitis, eosinophilic granuloma, allergic conjunctivitis, osteoarthritis; gastrointestinal inflammation diseases such as Crohn's disease, colitis, pancreatitis as well as different types of cancers including leukaemia; especially in humans. Processes for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds and their use as PDE type 4, PDE type 7 and dual PDE t e 4/PDE t e 7 inhibitors are rovided.

  本发明涉及磷酸二酯酶（PDE）4型、磷酸二酯酶（PDE）7型和双重PDE类型4/PDE类型7抑制剂。本文所披露的具有I式结构的化合物可用于治疗、预防、抑制或抑制中枢神经系统疾病，例如多发性硬化症；各种影响免疫系统的病理情况，包括艾滋病、移植排斥、自身免疫性疾病，如T细胞相关疾病，例如类风湿性关节炎；炎症性疾病，如呼吸道炎症性疾病，包括慢性阻塞性肺疾病（COPD）、哮喘、支气管炎、过敏性鼻炎、成人呼吸窘迫综合征（ARDS）以及其他炎症性疾病，包括但不限于牛皮癣、休克、特应性皮炎、嗜酸性肉芽肿、过敏性结膜炎、骨关节炎；胃肠道炎症性疾病，如克罗恩病、结肠炎、胰腺炎以及不同类型的癌症，包括白血病；特别是在人类中。本文提供了披露化合物的制备方法、含有披露化合物的制药组合物以及它们作为PDE类型4、PDE类型7和双重PDE类型4/PDE类型7抑制剂的用途。