4-nitro-1-phenylpyrazole-3-carbonitrile | 1426541-58-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-nitro-1-phenylpyrazole-3-carbonitrile
• 英文别名: 4-nitro-1-phenyl-1H-pyrazole-3-carbonitrile；4-Nitro-1-phenylpyrazole-3-carbonitrile
• CAS: 1426541-58-3
• 化学式: C₁₀H₆N₄O₂
• 分子量: 214.183
• InChiKey: FAPZQSKQUGPCSC-UHFFFAOYSA-N

物化性质

• 沸点：
  424.1±30.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-nitro-1-phenylpyrazole-3-carbonitrile 在 4-二甲氨基吡啶 、 1-hydroxybenzotriazole hydrochloride 、 palladium 10% on activated carbon 、 ammonium acetate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 环己烯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 168.58h， 生成 N-(5-methyl-2-phenylpyrazolo[4,3-d]pyrimidin-7-yl)-2-phenylacetamide
  参考文献：
  名称：

  2-Arylpyrazolo[4,3-d]pyrimidin-7-amino Derivatives As New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Molecular Modeling Studies and Pharmacological Evaluation

  摘要：

  On the basis of our previously reported 2-arylpyrazolo[4,3-d]pyrimidin-7-ones, a set of 2-arylpyrazolo[4,3- d]pyrimidin-7-amines were designed as new human (h) A(3) adenosine receptor (AR) antagonists. Lipophilic groups with different steric bulk were introduced at the 5-position of the bicyclic scaffold (R-5 = Me, Ph, CH2Ph), and different acyl and carbamoyl moieties (R-7) were appended on the 7-amino group, as well as a para-methoxy group inserted on the 2-phenyl ring. The presence of acyl groups turned out to be of paramount importance for an efficient and selective binding at the hA(3) AR In fact, most of the 7-acylamino derivatives showed low nanomolar affinity (K-l, = 2.5-45 nM) and high selectivity toward this receptor. A few selected pyrazolo[4,3-d]pyrimidin-7-amides were effective in counteracting oxaliplatin-induced apoptosis in rat astrocyte cell cultures, an in vitro model of neurotoxicity. Through an in silica receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA(3) AR affinity and hA(3) versus hA(2A) AR selectivity were explained.

  DOI：

  10.1021/jm400068e
• 作为产物：
  描述：

  ethyl (phenylhydrazono)chloroacetate 在 ammonium hydroxide 、 三乙胺 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 46.5h， 生成 4-nitro-1-phenylpyrazole-3-carbonitrile
  参考文献：
  名称：

  探索吡唑并[4,3-d]嘧啶-7-氨基支架的2位和5位靶向人A1和A2A腺苷受体。

  摘要：

  合成了一系列新的7-氨基吡唑并[4,3-d]嘧啶衍生物（1-31），以评估2位和5位的一些结构修饰，旨在改变对人（h）A2A腺苷受体（ AR）或hA2A和hA1 ARs。活性最高的化合物是那些在位置5处带有2-呋喃基或5-甲基呋喃-2-基的化合物，在位置2处带有苄基或取代的苄基，其中一些衍生物（22-31）具有纳摩尔浓度对hA2A AR的亲和力（Ki = 3.62-57nM），对hA1 AR的亲和力略低，因此显示出相对于hA1选择性而言，hA2A的程度不同（3-22倍）。尤其是，2-（2-甲氧基苄基）-5-（5-甲基呋喃-2-基）衍生物25具有最高的hA2A和hA1 AR亲和力（Ki = 3.62nM和18nM，并在这两个受体上均表现出强大的拮抗作用（cAMP分析）。它的2-（2-羟基苄基）类似物26对hA2A AR也有很高的亲和力（Ki = 5.26nM），相对于hA1亚型具有22倍的选择性。在hA2A

  DOI：

  10.1016/j.bmc.2016.04.048

文献信息

• The role of 5-arylalkylamino- and 5-piperazino- moieties on the 7-aminopyrazolo[4,3-<i>d</i>]pyrimidine core in affecting adenosine A₁ and A_2A receptor affinity and selectivity profiles
  作者：Lucia Squarcialupi、Marco Betti、Daniela Catarzi、Flavia Varano、Matteo Falsini、Annalisa Ravani、Silvia Pasquini、Fabrizio Vincenzi、Veronica Salmaso、Mattia Sturlese、Katia Varani、Stefano Moro、Vittoria Colotta

  DOI：10.1080/14756366.2016.1247060

  日期：2017.1.1

  New 7-amino-2-phenylpyrazolo[4,3-d]pyrimidine derivatives, substituted at the 5-position with aryl(alkyl)amino- and 4-substituted-piperazin-1-yl- moieties, were synthesized with the aim of targeting human (h) adenosine A1 and/or A2A receptor subtypes. On the whole, the novel derivatives 1-24 shared scarce or no affinities for the off-target hA2B and hA3 ARs. The 5-(4-hydroxyphenethylamino)- derivative

  合成了新的7-氨基-2-苯基吡唑并[4,3-d]嘧啶衍生物，该衍生物在5-位被芳基（烷基）氨基和4-取代的哌嗪-1-基部分取代，目的是：靶向人（h）腺苷A1和/或A2A受体亚型。总体而言，新的衍生物1-24对脱靶hA2B和hA3 ARs缺乏亲和力或没有亲和力。5-（4-羟基苯乙氨基）-衍生物12对hA2A AR表现出良好的亲和力（Ki = 150 nM）和最佳选择性，而5-苄基氨基取代的5显示出最佳的hA2A（Ki = 123 nM）和A1组合AR亲和力（Ki = 25 nM）。5-苯乙基氨基部分（化合物6）实现了纳摩尔亲和力（Ki = 11 nM）和对hA1 AR的良好选择性。5-（N4-取代的哌嗪-1-基）衍生物15-24以高纳摩尔范围内的亲和力结合hA1 AR亚型。
• Exploring the 2- and 5-positions of the pyrazolo[4,3-d]pyrimidin-7-amino scaffold to target human A1 and A2A adenosine receptors
  作者：Lucia Squarcialupi、Matteo Falsini、Daniela Catarzi、Flavia Varano、Marco Betti、Katia Varani、Fabrizio Vincenzi、Diego Dal Ben、Catia Lambertucci、Rosaria Volpini、Vittoria Colotta

  DOI：10.1016/j.bmc.2016.04.048

  日期：2016.6

  receptors (cAMP assays). Its 2-(2-hydroxybenzyl) analog 26 also showed a high affinity for the hA2A AR (Ki=5.26nM) and was 22-fold selective versus the hA1 subtype. Molecular docking investigations performed at the hA2A AR crystal structure and at a homology model of the hA1 AR allowed us to represent the hypothetical binding mode of our derivatives and to rationalize the observed SARs.

  合成了一系列新的7-氨基吡唑并[4,3-d]嘧啶衍生物（1-31），以评估2位和5位的一些结构修饰，旨在改变对人（h）A2A腺苷受体（ AR）或hA2A和hA1 ARs。活性最高的化合物是那些在位置5处带有2-呋喃基或5-甲基呋喃-2-基的化合物，在位置2处带有苄基或取代的苄基，其中一些衍生物（22-31）具有纳摩尔浓度对hA2A AR的亲和力（Ki = 3.62-57nM），对hA1 AR的亲和力略低，因此显示出相对于hA1选择性而言，hA2A的程度不同（3-22倍）。尤其是，2-（2-甲氧基苄基）-5-（5-甲基呋喃-2-基）衍生物25具有最高的hA2A和hA1 AR亲和力（Ki = 3.62nM和18nM，并在这两个受体上均表现出强大的拮抗作用（cAMP分析）。它的2-（2-羟基苄基）类似物26对hA2A AR也有很高的亲和力（Ki = 5.26nM），相对于hA1亚型具有22倍的选择性。在hA2A
• 2-Arylpyrazolo[4,3-<i>d</i>]pyrimidin-7-amino Derivatives As New Potent and Selective Human A₃ Adenosine Receptor Antagonists. Molecular Modeling Studies and Pharmacological Evaluation
  作者：Lucia Squarcialupi、Vittoria Colotta、Daniela Catarzi、Flavia Varano、Guido Filacchioni、Katia Varani、Carmen Corciulo、Fabrizio Vincenzi、Pier Andrea Borea、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Antonella Ciancetta、Stefano Moro

  DOI：10.1021/jm400068e

  日期：2013.3.28

  On the basis of our previously reported 2-arylpyrazolo[4,3-d]pyrimidin-7-ones, a set of 2-arylpyrazolo[4,3- d]pyrimidin-7-amines were designed as new human (h) A(3) adenosine receptor (AR) antagonists. Lipophilic groups with different steric bulk were introduced at the 5-position of the bicyclic scaffold (R-5 = Me, Ph, CH2Ph), and different acyl and carbamoyl moieties (R-7) were appended on the 7-amino group, as well as a para-methoxy group inserted on the 2-phenyl ring. The presence of acyl groups turned out to be of paramount importance for an efficient and selective binding at the hA(3) AR In fact, most of the 7-acylamino derivatives showed low nanomolar affinity (K-l, = 2.5-45 nM) and high selectivity toward this receptor. A few selected pyrazolo[4,3-d]pyrimidin-7-amides were effective in counteracting oxaliplatin-induced apoptosis in rat astrocyte cell cultures, an in vitro model of neurotoxicity. Through an in silica receptor-driven approach the obtained binding data were rationalized and the molecular bases of the observed hA(3) AR affinity and hA(3) versus hA(2A) AR selectivity were explained.