4-(4-(4-fluorophenyl)piperazin-1-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine | 393845-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-(4-fluorophenyl)piperazin-1-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-[4-(4-fluorophenyl)piperazin-1-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine；4-[4-(4-fluorophenyl)piperazin-1-yl]-1-phenylpyrazolo[3,4-d]pyrimidine
• CAS: 393845-82-4
• 化学式: C₂₁H₁₉FN₆
• 分子量: 374.42
• InChiKey: FBKAQSNYJGFXBM-UHFFFAOYSA-N

物化性质

• 沸点：
  535.2±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-氨基-4-乙氧羰基-1-苯基吡唑 在 三乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(4-(4-fluorophenyl)piperazin-1-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

  摘要：

  Four series of some 4‐substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine derivatives 5a–f, 6a–f, 8a–f, and 9a–f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF‐7) and lung (A‐549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR‐TK inhibitory activity where they revealed 41–91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP‐binding site of EGFR‐TK demonstrated their binding mode where H‐bonding interaction with Met793 through N1 of pyrimidine or N2 of pyrazole was observed.

  DOI：

  10.1111/cbdd.12451

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISEASE ASSOCIATED WITH TRP-P8 EXPRESSION
  申请人：Natarajan Sateesh K.

  公开号：US20120094977A1

  公开（公告）日：2012-04-19

  Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

  提供了小分子Trp-p8调节剂，包括Trp-p8激动剂和Trp-p8拮抗剂，以及包含小分子Trp-p8激动剂的组合物，以及用于识别和表征新型小分子Trp-p8调节剂的方法，以及用于降低Trp-p8表达细胞的存活率和/或抑制生长的方法，用于激活Trp-p8介导的阳离子流入的方法，用于刺激凋亡和/或坏死的方法，以及相关的治疗疾病的方法，包括肺癌、乳腺癌、结肠癌和/或前列腺癌等癌症，以及与Trp-p8表达相关的其他疾病，例如良性前列腺增生等。
• 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.
• US8389730B2
  申请人：——

  公开号：US8389730B2

  公开（公告）日：2013-03-05
• US8362264B2
  申请人：——

  公开号：US8362264B2

  公开（公告）日：2013-01-29
• 4-Substituted-1-phenyl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity
  作者：Safinaz E.-S. Abbas、Enayat I. Aly、Fadi M. Awadallah、Walaa R. Mahmoud

  DOI：10.1111/cbdd.12451

  日期：2015.5

  Four series of some 4‐substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine derivatives 5a–f, 6a–f, 8a–f, and 9a–f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF‐7) and lung (A‐549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR‐TK inhibitory activity where they revealed 41–91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP‐binding site of EGFR‐TK demonstrated their binding mode where H‐bonding interaction with Met793 through N1 of pyrimidine or N2 of pyrazole was observed.