4-(2-nitroethyl)pyrazolo[1,5-a]pyridine | 1276031-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 4-(2-nitroethyl)pyrazolo[1,5-a]pyridine
• CAS: 1276031-72-1
• 化学式: C₉H₉N₃O₂
• 分子量: 191.189
• InChiKey: AFNUBSPSXGMPKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  63.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-nitroethyl)pyrazolo[1,5-a]pyridine 、 N,N-二甲基甲酰胺 在 三氯氧磷 、 水 作用下， 反应 0.75h， 生成
  参考文献：
  名称：

  Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D₃ Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions

  摘要：

  Heterocyclic dopamine surrogates of types 5 and 7 were synthesized and investigated for their dopaminergic properties. The enantiomerically pure biphenylcarboxamide (S)-5a displayed an outstanding K-i of 27 pM at the agonist-labeled D-3 receptor and significant selectivity over the D-2 subtype. Measurement of [S-35]GTP gamma S incorporation in the presence of a coexpressed PTX-insensitive G(alpha 0-1) subunit indicated highly efficient G-protein coupling. Comparison of ligand efficacy data from cAMP accumulation and [H-3]thymidine incorporation experiments revealed that ligand biased signaling is exerted by the test compound (S)-5a. Starting from the D-3 crystal structure, a combination of homology modeling and site directed mutagenesis gave valuable insights into the binding mode and the intermolecular origins of stereospecific receptor recognition. According to these data, the superior affinity of the eutomer 5a is caused by the favorable binding energy that results from interaction between the ligand's central ammonium unit and the aspartate residue in position 3.32 of the receptor.

  DOI：

  10.1021/jm101639t
• 作为产物：
  描述：

  4-(2-nitrovinyl)pyrazolo[1,5-a]pyridine 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以82%的产率得到4-(2-nitroethyl)pyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D₃ Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions

  摘要：

  Heterocyclic dopamine surrogates of types 5 and 7 were synthesized and investigated for their dopaminergic properties. The enantiomerically pure biphenylcarboxamide (S)-5a displayed an outstanding K-i of 27 pM at the agonist-labeled D-3 receptor and significant selectivity over the D-2 subtype. Measurement of [S-35]GTP gamma S incorporation in the presence of a coexpressed PTX-insensitive G(alpha 0-1) subunit indicated highly efficient G-protein coupling. Comparison of ligand efficacy data from cAMP accumulation and [H-3]thymidine incorporation experiments revealed that ligand biased signaling is exerted by the test compound (S)-5a. Starting from the D-3 crystal structure, a combination of homology modeling and site directed mutagenesis gave valuable insights into the binding mode and the intermolecular origins of stereospecific receptor recognition. According to these data, the superior affinity of the eutomer 5a is caused by the favorable binding energy that results from interaction between the ligand's central ammonium unit and the aspartate residue in position 3.32 of the receptor.

  DOI：

  10.1021/jm101639t