ethyl 5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-2-carboxylate | 1610742-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-2-carboxylate
• 英文别名: Ethyl 5-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]pyrazolo[1,5-a]pyridine-2-carboxylate；ethyl 5-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]pyrazolo[1,5-a]pyridine-2-carboxylate
• CAS: 1610742-45-4
• 化学式: C₂₄H₂₈Cl₂N₄O₃
• 分子量: 491.417
• InChiKey: HXHZPLKJASKRCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-2-carboxylate 在 盐酸 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 盐酸羟胺 、 sodium hydroxide 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-2-carbaldehyde oxime
  参考文献：
  名称：

  Functionally Selective Dopamine D₂, D₃Receptor Partial Agonists

  摘要：

  Dopamine D-2 receptor-promoted activation of G alpha(o) over G alpha(i) may increase synaptic plasticity and thereby might improve negative symptoms of schizophrenia. Heterocyclic dopamine surrogates comprising a pyrazolo[1,5-a]pyridine moiety were synthesized and investigated for their binding properties when low- to subnanomolar K-i values were determined for D-2L, D-2S, and D-3 receptors. Measurement of [S-35]GTP gamma S incorporation at D-2S coexpressed with G-protein subunits indicated significant bias for promotion of G alpha(o1) over G alpha(i2) coupling for several test compounds. Functionally selective D-2S activation was most striking for the carbaldoxime 8b (G alpha(o1), pEC(50) = 8.87, E-max = 65%; G alpha(i2), pEC(50) = 6.63, E-max = 27%). In contrast, the investigated 1,4-disubstituted aromatic piperazines (1,4-DAPs) behaved as antagonists for beta-arrestin-2 recruitment, implying significant ligand bias for G-protein activation over beta-arrestin-2 recruitment at D-2S receptors. Ligand efficacy and selectivity between D-2S and D-3 activation were strongly influenced by regiochemistry and the nature of functional groups attached to the pyrazolo[1,5-a]pyridine moiety.

  DOI：

  10.1021/jm5004039
• 作为产物：
  描述：

  ethyl 5-hydroxypyrazolo[1,5-a]pyridine-2-carboxylate 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.5h， 生成 ethyl 5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-2-carboxylate
  参考文献：
  名称：

  Functionally Selective Dopamine D₂, D₃Receptor Partial Agonists

  摘要：

  Dopamine D-2 receptor-promoted activation of G alpha(o) over G alpha(i) may increase synaptic plasticity and thereby might improve negative symptoms of schizophrenia. Heterocyclic dopamine surrogates comprising a pyrazolo[1,5-a]pyridine moiety were synthesized and investigated for their binding properties when low- to subnanomolar K-i values were determined for D-2L, D-2S, and D-3 receptors. Measurement of [S-35]GTP gamma S incorporation at D-2S coexpressed with G-protein subunits indicated significant bias for promotion of G alpha(o1) over G alpha(i2) coupling for several test compounds. Functionally selective D-2S activation was most striking for the carbaldoxime 8b (G alpha(o1), pEC(50) = 8.87, E-max = 65%; G alpha(i2), pEC(50) = 6.63, E-max = 27%). In contrast, the investigated 1,4-disubstituted aromatic piperazines (1,4-DAPs) behaved as antagonists for beta-arrestin-2 recruitment, implying significant ligand bias for G-protein activation over beta-arrestin-2 recruitment at D-2S receptors. Ligand efficacy and selectivity between D-2S and D-3 activation were strongly influenced by regiochemistry and the nature of functional groups attached to the pyrazolo[1,5-a]pyridine moiety.

  DOI：

  10.1021/jm5004039

文献信息

• Functionally Selective Dopamine D₂, D₃Receptor Partial Agonists
  作者：Dorothee Möller、Ralf C. Kling、Marika Skultety、Kristina Leuner、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm5004039

  日期：2014.6.12

  Dopamine D-2 receptor-promoted activation of G alpha(o) over G alpha(i) may increase synaptic plasticity and thereby might improve negative symptoms of schizophrenia. Heterocyclic dopamine surrogates comprising a pyrazolo[1,5-a]pyridine moiety were synthesized and investigated for their binding properties when low- to subnanomolar K-i values were determined for D-2L, D-2S, and D-3 receptors. Measurement of [S-35]GTP gamma S incorporation at D-2S coexpressed with G-protein subunits indicated significant bias for promotion of G alpha(o1) over G alpha(i2) coupling for several test compounds. Functionally selective D-2S activation was most striking for the carbaldoxime 8b (G alpha(o1), pEC(50) = 8.87, E-max = 65%; G alpha(i2), pEC(50) = 6.63, E-max = 27%). In contrast, the investigated 1,4-disubstituted aromatic piperazines (1,4-DAPs) behaved as antagonists for beta-arrestin-2 recruitment, implying significant ligand bias for G-protein activation over beta-arrestin-2 recruitment at D-2S receptors. Ligand efficacy and selectivity between D-2S and D-3 activation were strongly influenced by regiochemistry and the nature of functional groups attached to the pyrazolo[1,5-a]pyridine moiety.