4-nitro-2-phenylpyrazole-5-carboxamide | 1190306-10-5

• 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-2-phenylpyrazole-5-carboxamide
• 英文别名: 4-Nitro-1-phenylpyrazole-3-carboxamide
• CAS: 1190306-10-5
• 化学式: C₁₀H₈N₄O₃
• 分子量: 232.199
• InChiKey: FUYGKCBUJWBOAG-UHFFFAOYSA-N

物化性质

• 熔点：
  230-232 °C(Solvent: Glycol monoethyl ether)
• 沸点：
  434.8±25.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-nitro-2-phenylpyrazole-5-carboxamide 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 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 169.08h， 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 作用下， 以 氯仿 为溶剂， 反应 46.5h， 生成 4-nitro-2-phenylpyrazole-5-carboxamide
  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

• 2-Phenylpyrazolo[4,3-<i>d</i>]pyrimidin-7-one as a New Scaffold To Obtain Potent and Selective Human A₃ Adenosine Receptor Antagonists: New Insights into the Receptor−Antagonist Recognition
  作者：Ombretta Lenzi、Vittoria Colotta、Daniela Catarzi、Flavia Varano、Daniela Poli、Guido Filacchioni、Katia Varani、Fabrizio Vincenzi、Pier Andrea Borea、Silvia Paoletta、Erika Morizzo、Stefano Moro

  DOI：10.1021/jm900718w

  日期：2009.12.10

  A molecular simplification approach of previously reported 2-arylpyrazolo[3,4-c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d]pyrimidin-7-one derivatives as new human A(3) adenosine receptor antagonists. Substituents with different lipophilicity and steric hindrance were introduced at the 5-position of the bicyclic Scaffold (R-5 = H, Me, Et, Ph, CH2Ph) and on the 2-phenyl ring (OMe, Me). Most of the synthesized derivatives were highly potent hA(3) adenosine receptor antagonists, the best being the 2-(4-methoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-one (K-i = 1.2 nM). The new compounds were also highly selective, being completely devoid of affinity toward hA(1), hA(2A), and hA(2B) adenosine receptors. On the basis of the recently published human A(2A) receptor crystallographic information, we propose it novel receptor-driven hypothesis to explain both A(3) AR affinity and A(3) versus A(2A) Selectivity profiles of these new antagonists.
• 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.