4,5,6,7-tetrafluoro-1H-indazole | 1294396-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4,5,6,7-tetrafluoro-1H-indazole
• CAS: 1294396-96-5
• 化学式: C₇H₂F₄N₂
• 分子量: 190.1
• InChiKey: GBQVJKBTDYRAQN-UHFFFAOYSA-N

物化性质

• 沸点：
  273.8±35.0 °C(Predicted)
• 密度：
  1.698±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,5,6,7-tetrafluoro-1H-indazole 在 盐酸 、 三乙胺 、 三氟乙酸 、 mercury dichloride 、 sodium hydroxide 、 hydroxylamine-O-sulfonic acid 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.83h， 生成 4,5,6,7-tetrafluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole hydrochloride
  参考文献：
  名称：

  Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities

  摘要：

  The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective alpha(2)-aradrenoceptor (alpha(2)-AR) agonists: 1-[(imidazolidin-2-yl) imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and alpha(2)-AR/I-1 imidazoline binding site selectivity. The most alpha(2)-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d). The in vivo cardiovascular properties of fluorinated derivatives of A and B revealed that in both cases the C-7 fluorination leads to compounds with the highest hypotensive and bradycardic activities. The alpha(2)-AR partial agonist 6c was prepared as a potential lead compound for development of a radiotracer for PET imaging of brain alpha(2)-ARs. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.083
• 作为产物：
  描述：

  2',3',4',5',6'-五氟苯乙酮 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以13%的产率得到4,5,6,7-tetrafluoro-1H-indazole
  参考文献：
  名称：

  Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities

  摘要：

  The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective alpha(2)-aradrenoceptor (alpha(2)-AR) agonists: 1-[(imidazolidin-2-yl) imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and alpha(2)-AR/I-1 imidazoline binding site selectivity. The most alpha(2)-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d). The in vivo cardiovascular properties of fluorinated derivatives of A and B revealed that in both cases the C-7 fluorination leads to compounds with the highest hypotensive and bradycardic activities. The alpha(2)-AR partial agonist 6c was prepared as a potential lead compound for development of a radiotracer for PET imaging of brain alpha(2)-ARs. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.083

文献信息

• Synthesis and biological evaluation of indazole derivatives
  作者：Rosa M. Claramunt、Concepción López、Ana López、Carlos Pérez-Medina、Marta Pérez-Torralba、Ibon Alkorta、José Elguero、Germaine Escames、Darío Acuña-Castroviejo

  DOI：10.1016/j.ejmech.2011.01.027

  日期：2011.4

  and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference, Erel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.

  已经评估了一系列36种吲唑对神经元和诱导型一氧化氮合酶（nNOS和iNOS）的抑制作用，表明大多数被测定的衍生物比nNOS抑制剂具有更好的iNOS。建立了一个iNOS抑制百分率与吲唑的堆积和根尖相互作用能与NOS酶活性位点之间的差E rel的抛物线模型。
• Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities
  作者：Aleksandra Wasilewska、Franciszek Sączewski、Alan L. Hudson、Mehnaz Ferdousi、Mika Scheinin、Jonne M. Laurila、Apolonia Rybczyńska、Konrad Boblewski、Artur Lehmann

  DOI：10.1016/j.ejmech.2014.09.083

  日期：2014.11

  The aim of these studies was to establish the influence of fluorination of the indazole ring on the pharmacological properties of two selective alpha(2)-aradrenoceptor (alpha(2)-AR) agonists: 1-[(imidazolidin-2-yl) imino]-1H-indazole (marsanidine, A) and its methylene analogue 1-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-1H-indazole (B). Introduction of fluorine into the indazole ring of A and B reduced both binding affinity and alpha(2)-AR/I-1 imidazoline binding site selectivity. The most alpha(2)-AR-selective ligands were 6-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6c) and 7-fluoro-1-[(imidazolidin-2-yl)imino]-1H-indazole (6d). The in vivo cardiovascular properties of fluorinated derivatives of A and B revealed that in both cases the C-7 fluorination leads to compounds with the highest hypotensive and bradycardic activities. The alpha(2)-AR partial agonist 6c was prepared as a potential lead compound for development of a radiotracer for PET imaging of brain alpha(2)-ARs. (C) 2014 Elsevier Masson SAS. All rights reserved.