N-cycloheptyl-4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine | 1410219-43-0

• 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: N-cycloheptyl-4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine
• CAS: 1410219-43-0
• 化学式: C₁₈H₂₁N₇O
• 分子量: 351.411
• InChiKey: NNXMGTRINHPQFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]-1-methyl-1H-pyrazol-3-amine 在 吡啶 、 五氯化磷 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 27.5h， 生成 N-cycloheptyl-4-(furan-2-yl)-11-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaen-7-amine
  参考文献：
  名称：

  Exploring the Directionality of 5-Substitutions in a New Series of 5-Alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine as a Strategy To Design Novel Human A₃ Adenosine Receptor Antagonists.

  摘要：

  The structure-activity relationship (SAR) of new 5-alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines as antagonists of the A(3) adenosine receptor (AR) was explored with the principal aim to establish the directionality of 5-substitutions inside the orthosteric binding site of the A(3) AR. All the synthesized compounds showed affinity for the hA(3) AR from nanomolar to subnanomolar range. In particular, the most potent and selective antagonist presents an (S) alpha-phenylethylamino moiety at the 5 position (26, K-i hA(3) = 0.3 nM). Using an in silico receptor-driven approach, we have determined the most favorable orientation of the substitutions at the 5 position of the pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) scaffold, opening the possibility for further derivatizations aimed at directing the N-5 position toward the extracellular environment.

  DOI：

  10.1021/jm300899q

文献信息

• Exploring the Directionality of 5-Substitutions in a New Series of 5-Alkylaminopyrazolo[4,3-<i>e</i>]1,2,4-triazolo[1,5-<i>c</i>]pyrimidine as a Strategy To Design Novel Human A₃ Adenosine Receptor Antagonists.
  作者：Stephanie Federico、Antonella Ciancetta、Davide Sabbadin、Silvia Paoletta、Giorgia Pastorin、Barbara Cacciari、Karl Norbert Klotz、Stefano Moro、Giampiero Spalluto

  DOI：10.1021/jm300899q

  日期：2012.11.26

  The structure-activity relationship (SAR) of new 5-alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines as antagonists of the A(3) adenosine receptor (AR) was explored with the principal aim to establish the directionality of 5-substitutions inside the orthosteric binding site of the A(3) AR. All the synthesized compounds showed affinity for the hA(3) AR from nanomolar to subnanomolar range. In particular, the most potent and selective antagonist presents an (S) alpha-phenylethylamino moiety at the 5 position (26, K-i hA(3) = 0.3 nM). Using an in silico receptor-driven approach, we have determined the most favorable orientation of the substitutions at the 5 position of the pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) scaffold, opening the possibility for further derivatizations aimed at directing the N-5 position toward the extracellular environment.