1-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-ol | 1197864-10-0

• 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-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-ol
• 英文别名: 1-(1-Phenylpyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-ol
• CAS: 1197864-10-0
• 化学式: C₁₆H₁₇N₅O
• 分子量: 295.344
• InChiKey: WCJBSKDRWXSDQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-1-苯基-1H-吡唑并[3,4-d]嘧啶 在 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 4.0h， 生成 1-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-ol
  参考文献：
  名称：

  Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design, synthesis and biological evaluation as potential anti-inflammatory agents

  摘要：

  A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated as potential anti-inflammatory agents. The newly prepared compounds were assessed through the examination of their in vitro inhibition of four targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappa B). Compounds 8a, 10c and 13c were the most potent and selective ligands against COX-2 with inhibition percentages of 79.6%, 78.7% and 78.9% at a concentration of 2 mu M respectively, while compound 13c significantly inhibited both COX subtypes. On the other hand, fourteen compounds showed high iNOS inhibitory activities with IC50 values in the range of 0.22-8.5 mu M where the urea derivative 11 was the most active compound with IC50 value of 0.22 mu M. Most of the tested compounds were found to be devoid of inhibitory activity against NF-kappa B. Moreover, almost all compounds were not cytotoxic, (up to 25 mu g/ml), against a panel of normal and cancer cell lines. The in silico docking results were in agreement with the in vitro inhibitory activities against COXs and iNOS enzymes. The results of in vivo anti-inflammatory and antinociceptive studies were consistent with that of in vitro studies which confirmed that compounds 8a, 10c and 13c have significant anti-inflammatory and analgesic activities comparable to that of the control, ketorolac. Taken together, dual inhibition of COXs and iNOS with novel pyrazolopyrimidine derivatives is a valid strategy for the development of anti-inflammatory/analgesic agents with the probability of fewer side effects. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2014.05.025

文献信息

• Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design, synthesis and biological evaluation as potential anti-inflammatory agents
  作者：Ahmed H. Abdelazeem、Shaimaa A. Abdelatef、Mohammed T. El-Saadi、Hany A. Omar、Shabana I. Khan、Christopher R. McCurdy、Samir M. El-Moghazy

  DOI：10.1016/j.ejps.2014.05.025

  日期：2014.10

  A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated as potential anti-inflammatory agents. The newly prepared compounds were assessed through the examination of their in vitro inhibition of four targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappa B). Compounds 8a, 10c and 13c were the most potent and selective ligands against COX-2 with inhibition percentages of 79.6%, 78.7% and 78.9% at a concentration of 2 mu M respectively, while compound 13c significantly inhibited both COX subtypes. On the other hand, fourteen compounds showed high iNOS inhibitory activities with IC50 values in the range of 0.22-8.5 mu M where the urea derivative 11 was the most active compound with IC50 value of 0.22 mu M. Most of the tested compounds were found to be devoid of inhibitory activity against NF-kappa B. Moreover, almost all compounds were not cytotoxic, (up to 25 mu g/ml), against a panel of normal and cancer cell lines. The in silico docking results were in agreement with the in vitro inhibitory activities against COXs and iNOS enzymes. The results of in vivo anti-inflammatory and antinociceptive studies were consistent with that of in vitro studies which confirmed that compounds 8a, 10c and 13c have significant anti-inflammatory and analgesic activities comparable to that of the control, ketorolac. Taken together, dual inhibition of COXs and iNOS with novel pyrazolopyrimidine derivatives is a valid strategy for the development of anti-inflammatory/analgesic agents with the probability of fewer side effects. (C) 2014 Elsevier B.V. All rights reserved.