2-Phenyl-2H-pyrazolo[3,4-c]quinolin-4-ylamine | 298201-68-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-Phenyl-2H-pyrazolo[3,4-c]quinolin-4-ylamine
• 英文别名: 2-phenyl-2H-pyrazolo[3,4-c]quinolin-4-amine；2-phenylpyrazolo[3,4-c]quinolin-4-amine
• CAS: 298201-68-0
• 化学式: C₁₆H₁₂N₄
• 分子量: 260.298
• InChiKey: MVHJGGYPZDDBQV-UHFFFAOYSA-N

物化性质

• 熔点：
  198-199 °C(Solv: ethyl acetate (141-78-6))
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-二苯基乙酸 、 2-Phenyl-2H-pyrazolo[3,4-c]quinolin-4-ylamine 在 4-二甲氨基吡啶 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以44%的产率得到2,2-diphenyl-N-(2-phenyl-2H-pyrazolo[3,4-c]quinolin-4-yl)acetamide
  参考文献：
  名称：

  New 2-Arylpyrazolo[3,4-c]quinoline Derivatives as Potent and Selective Human A₃ Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation, and Ligand−Receptor Modeling Studies

  摘要：

  This paper reports the study of some 2-arylpyrazolo[3,4-c]quinolin-4-ones, 4-amines, and 4-amino-substituted derivatives designed as human A(3) adenosine receptor (AR) antagonists. Most of the herein reported compounds showed a nanomolar affinity toward the hA(3) receptor subtype and different degrees of selectivity that resulted to be strictly dependent on the presence and nature of the substituent on the 4-amino group. Bulky and lipophilic acyl groups, as well as the benzylcarbamoyl residue, afforded highly potent and selective hA(3) receptor antagonists. The selected 4-diphenylacetylamino-2-phenylpyrazoloquinoline (25) and 4-dibenzoylamino-2-(4-methoxyphenyl)pyrazoloquinoline (36), tested in an in vitro rat model of cerebral ischemia, prevented the irreversible failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. The observed structure-affinity relationships of this class of antagonists were also exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach.

  DOI：

  10.1021/jm070123v
• 作为产物：
  描述：

  2-phenylpyrazolo[3,4-c]quinolin-4(5H)-one 在 五氯化磷 、 环己胺 、 三氯氧磷 作用下， 反应 1.0h， 生成 2-Phenyl-2H-pyrazolo[3,4-c]quinolin-4-ylamine
  参考文献：
  名称：

  一组新的2-芳基吡唑并[3,4-c]喹啉衍生物作为腺苷受体拮抗剂的合成与构效关系。

  摘要：

  在最近的一篇论文中（Colotta等人，J。Med。Chem。2000，43，1158-1164），我们报道了两组2-芳基-1,2,4-三唑并[4,3,3,4,3,3,4,3,3,4,3,3,3,3,3,3,3,4,3,4,3,3,4,3]的合成和腺苷受体结合活性。 3-a]喹喔啉（A和B），其中一些是有效的和选择性的A（1）或A（3）拮抗剂。在本文中，报道了一组2-芳基吡唑并[3,4-c]喹啉-4-酮1-10、4-胺11-18和4-氨基取代的衍生物19-35的合成。在牛A（1）和A（2A）以及人类克隆的A（3）腺苷受体上的结合活性表明（i）附加的2-苯环上的取代基可用于调节A（1）和A（3） ）亲和力；（ii）4-氨基对于A（1）和A（2A）的结合活性必不可少，并且（iii）4位的核或核外C = O质子受体产生有效且有选择性的A（3）拮抗剂。这些结果与先前报道的系列A和B的结果一致，表明

  DOI：

  10.1021/jm000936i

文献信息

• Novel potent and highly selective human A3 adenosine receptor antagonists belonging to the 4-amido-2-arylpyrazolo[3,4-c]quinoline series: Molecular docking analysis and pharmacological studies
  作者：Vittoria Colotta、Francesca Capelli、Ombretta Lenzi、Daniela Catarzi、Flavia Varano、Daniela Poli、Fabrizio Vincenzi、Katia Varani、Pier Andrea Borea、Diego Dal Ben、Rosaria Volpini、Gloria Cristalli、Guido Filacchioni

  DOI：10.1016/j.bmc.2008.10.018

  日期：2009.1

  The study of novel 2-arylpyrazolo[3,4-c]quinolin-4-(hetero)arylamides, designed as human (h) A(3) adenosine receptor antagonists, is reported. The new derivatives are endowed with nanomolar hA(3) receptor affinity and high selectivity versus hA(1), hA(2A) and hA(2B) receptors. Among the (hetero) aroyl residues introduced on the 4-amino group, the 2-furyl and 4-pyridyl rings turned out to be the most beneficial for hA(3) affinity (K-i = 3.4 and 5.0 nM, respectively). An intensive molecular docking study to a rhodopsin-based homology model of the hA(3) receptor was carried out to obtain a 'structure-based pharmacophore model' that proved to be helpful for the interpretation of the observed affinities of the new hA(3) pyrazoloquino-line antagonists. (C) 2008 Elsevier Ltd. All rights reserved.