1,3,5-trimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1,3,5-trimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
• 英文别名: 1,3,5-Trimethyl-6-phenyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione；1,3,5-trimethyl-6-phenylpyrrolo[3,2-d]pyrimidine-2,4-dione
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: QGQWRPICURFNAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 哌啶 、 硫酸 、 硝酸 、 potassium carbonate 、 亚磷酸三乙酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1,3,5-trimethyl-6-phenyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Deazaxanthines: Analogs of Potent A1- and A2-Adenosine Receptor Antagonists

  摘要：

  A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d] pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9-Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 2-3-fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2-naphthyl)-9-deazaxanthine (19e) showed high affinty (K-i = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9-deazaxanthines was unfavorable for A1 and A2a receptor binding. 7-Deazaxanthines were considerably less potent compared to xanthines and to 9-deazaxanthines at both receptor subtypes.

  DOI：

  10.1021/jm00036a019

文献信息

• Divergent synthesis of novel 9-deazaxanthine derivatives via late-stage cross-coupling reactions
  作者：Francesca Bartoccini、Giovanni Piersanti、Marco Mor、Giorgio Tarzia、Patrizia Minetti、Walter Cabri

  DOI：10.1039/c2ob26516h

  日期：——

  A small library of 8-substituted 9-deazaxanthines has been prepared by late-stage diversification of an 8-bromo-9-deazaxanthine. By utilizing palladium-catalyzed cross-coupling reactions a single key precursor can be transformed into a variety of 8-substituted-9-deazaxanthine compounds. Three key 8-bromo-9-deazaxanthine intermediates were efficiently prepared from commercially available 6-chlorouracil in six steps.

  通过对8-溴-9-去氨黄素的后期多样化，制备了一小库8-取代的9-去氨黄素。利用钯催化的交叉偶联反应，可以将一个单一的关键前体转化为多种8-取代的9-去氨黄素化合物。三个关键的8-溴-9-去氨黄素中间体通过六步反应高效地从商业可得的6-氯尿嘧啶制备而成。
• 8-Substituted-9-deazaxanthines as adenosine receptor ligands: design, synthesis and structure-affinity relationships at A2B
  作者：Angelo Carotti、Angela Stefanachi、Enrique Raviña、Eddy Sotelo、Maria Isabel Loza、Maria Isabel Cadavid、Nuria B. Centeno、Orazio Nicolotti

  DOI：10.1016/j.ejmech.2004.07.008

  日期：2004.10

  A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6-substituted-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-diones) were prepared and tested for their antagonistic activity at the recombinant human adenosine receptors, in particular at the A(2B) and A(2A) receptor subtypes. Compounds endowed with micromolar to nanomolar binding affinities, but with poor A(2B)/A(2A) selectivity, were obtained. Preliminary quantitative structure-affinity relationships suggested that the binding potency at the A(2B) receptor is mainly modulated by the electronic and lipophilic properties of the ligands. (C) 2004 Elsevier SAS. All rights reserved.
• Synthesis and Structure-Activity Relationships of Deazaxanthines: Analogs of Potent A1- and A2-Adenosine Receptor Antagonists
  作者：Bettina Grahner、Susanne Winiwarter、Wolfgang Lanzner、Christa E. Mueller

  DOI：10.1021/jm00036a019

  日期：1994.5

  A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d] pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9-Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 2-3-fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2-naphthyl)-9-deazaxanthine (19e) showed high affinty (K-i = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9-deazaxanthines was unfavorable for A1 and A2a receptor binding. 7-Deazaxanthines were considerably less potent compared to xanthines and to 9-deazaxanthines at both receptor subtypes.