2-phenyl-9-(2-fluorobenzyl)-8-azaadenine | 860470-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 2-phenyl-9-(2-fluorobenzyl)-8-azaadenine
• 英文别名: 9-(Ortho-fluorobenzyl)-2-phenyl-azaadenine (1bis)；3-[(2-fluorophenyl)methyl]-5-phenyltriazolo[4,5-d]pyrimidin-7-amine
• CAS: 860470-44-6
• 化学式: C₁₇H₁₃FN₆
• 分子量: 320.329
• InChiKey: NXRBUSNWTZFORH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  82.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-phenyl-9-(2-fluorobenzyl)-8-azaadenine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 异丙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 3-amino-N-[3-[(2-fluorophenyl)methyl]-5-phenyltriazolo[4,5-d]pyrimidin-7-yl]benzamide
  参考文献：
  名称：

  N-[9-(ortho-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides as Potent and Selective Ligands for A₁Adenosine Receptors

  摘要：

  A series of N‐[9‐(ortho‐fluorobenzyl)‐2‐phenyl‐8‐azapurin‐6‐yl]‐amides were synthesized and tested for their affinity toward A1, A2A, and A3 adenosine receptor subtypes. Biological results demonstrated that the introduction of a fluorine atom at the ortho position of the 9‐benzyl group generally enhanced affinity toward A1 subtype and did not significantly affect A2A and A3 affinity. Very interesting is the compound bearing a meta‐fluorophenyl substituent on the carbonyl carbon of the amide group, which shows significantly high A1/A2A‐A3 selectivity. Compounds of this new series, together with the previously published analogs without the fluorine atom on the 9‐benzyl group, constituted the starting dataset for the development of QSAR models. The models obtained were able to rationally describe the affinity trends resulting from biological testing and to enable investigation of the role of different substituents on the 8‐azapurine scaffold, as well as the influence of the newly introduced fluorine atom on the benzyl moiety. The said QSAR models can also assist in the design of new compounds selectively active on A1 adenosine receptors. Furthermore, a molecular docking study was carried out to assess hypothetical binding mode of N‐[9‐(ortho‐fluorobenzyl)‐2‐phenyl‐8‐azapurin‐6‐yl]‐amides to A1 adenosine receptors.

  DOI：

  10.1111/cbdd.12131
• 作为产物：
  描述：

  7-Chloro-3-(2-fluoro-benzyl)-5-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine 在 氨 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 2-phenyl-9-(2-fluorobenzyl)-8-azaadenine
  参考文献：
  名称：

  2,9-Disubstituted-N6-(arylcarbamoyl)-8-azaadenines as new selective A3 adenosine receptor antagonists: Synthesis, biochemical and molecular modelling studies

  摘要：

  A number of N-6-(N-arylcarbamoyl)-2-substituted-9-benzyl-8-azaadenines, obtained by a modification of the synthetic scheme used to prepare selective A(1) ligands, by only three or two steps, are described. At first we prepared a series of 2-phenyl-9-benzyl-8-azaadenines having as N-6 substituent a variously substituted N-phenylcarbamoyl group. Some of these derivatives demonstrated good affinity towards the A(3) subtype but low selectivity. Compounds having p-CF3, p-F and p-OCH3, as substituents on the phenylcarbamoyl group were selected as lead compounds for the second part of this study. Without modifying the N-6 substituent, which would assure A(3) affinity, we varied the 9 and 2 positions on these molecules to enhance selectivity. Some compounds having a p-methyl group on the 2-phenyl substituent showed a very good affinity and selectivity for the A(3) subtype, revealing the first class of A(3) adenosine receptor selective antagonists with a bicyclic structure strictly correlated to the adenine nucleus. The molecular modelling work, carried out using the DOCK program, supplied two models which may be useful for a better understanding of the binding modes. Both models highlighted the preferred interacting tautomeric forms of the antagonists for human A(1) and A(3) receptors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.063

文献信息

• 2,9-Disubstituted-N6-(arylcarbamoyl)-8-azaadenines as new selective A3 adenosine receptor antagonists: Synthesis, biochemical and molecular modelling studies
  作者：Giuliana Biagi、Anna Maria Bianucci、Alessio Coi、Barbara Costa、Laura Fabbrini、Irene Giorgi、Oreste Livi、Iolanda Micco、Federica Pacchini、Edoardo Santini、Michele Leonardi、Fatena Ahmad Nofal、Oreste LeRoy Salerni、Valerio Scartoni

  DOI：10.1016/j.bmc.2005.04.063

  日期：2005.8

  A number of N-6-(N-arylcarbamoyl)-2-substituted-9-benzyl-8-azaadenines, obtained by a modification of the synthetic scheme used to prepare selective A(1) ligands, by only three or two steps, are described. At first we prepared a series of 2-phenyl-9-benzyl-8-azaadenines having as N-6 substituent a variously substituted N-phenylcarbamoyl group. Some of these derivatives demonstrated good affinity towards the A(3) subtype but low selectivity. Compounds having p-CF3, p-F and p-OCH3, as substituents on the phenylcarbamoyl group were selected as lead compounds for the second part of this study. Without modifying the N-6 substituent, which would assure A(3) affinity, we varied the 9 and 2 positions on these molecules to enhance selectivity. Some compounds having a p-methyl group on the 2-phenyl substituent showed a very good affinity and selectivity for the A(3) subtype, revealing the first class of A(3) adenosine receptor selective antagonists with a bicyclic structure strictly correlated to the adenine nucleus. The molecular modelling work, carried out using the DOCK program, supplied two models which may be useful for a better understanding of the binding modes. Both models highlighted the preferred interacting tautomeric forms of the antagonists for human A(1) and A(3) receptors. (c) 2005 Elsevier Ltd. All rights reserved.
• <i>N</i>-[9-(<i>ortho</i>-Fluorobenzyl)-2-Phenyl-8-Azapurin-6-yl]-Amides as Potent and Selective Ligands for A₁Adenosine Receptors
  作者：Alice Borghini、Daniele Pietra、Michele Leonardi、Irene Giorgi、Anna M. Bianucci

  DOI：10.1111/cbdd.12131

  日期：2013.7

  A series of N‐[9‐(ortho‐fluorobenzyl)‐2‐phenyl‐8‐azapurin‐6‐yl]‐amides were synthesized and tested for their affinity toward A1, A2A, and A3 adenosine receptor subtypes. Biological results demonstrated that the introduction of a fluorine atom at the ortho position of the 9‐benzyl group generally enhanced affinity toward A1 subtype and did not significantly affect A2A and A3 affinity. Very interesting is the compound bearing a meta‐fluorophenyl substituent on the carbonyl carbon of the amide group, which shows significantly high A1/A2A‐A3 selectivity. Compounds of this new series, together with the previously published analogs without the fluorine atom on the 9‐benzyl group, constituted the starting dataset for the development of QSAR models. The models obtained were able to rationally describe the affinity trends resulting from biological testing and to enable investigation of the role of different substituents on the 8‐azapurine scaffold, as well as the influence of the newly introduced fluorine atom on the benzyl moiety. The said QSAR models can also assist in the design of new compounds selectively active on A1 adenosine receptors. Furthermore, a molecular docking study was carried out to assess hypothetical binding mode of N‐[9‐(ortho‐fluorobenzyl)‐2‐phenyl‐8‐azapurin‐6‐yl]‐amides to A1 adenosine receptors.