2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine | 1060725-14-5

• 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: 2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine
• 英文别名: 2-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]pyrazolo[1,5-a]pyridine；2-[4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butoxy]pyrazolo[1,5-a]pyridine
• CAS: 1060725-14-5
• 化学式: C₂₁H₂₄Cl₂N₄O
• 分子量: 419.354
• InChiKey: ANOQJCMMWZANCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine 、 N,N-二甲基甲酰胺 在 三氯氧磷 、 水 作用下， 反应 1.0h， 以70%的产率得到2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine-3-carbaldehyde
  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：

  吡唑并[1,5-a]吡啶-2(1H)-酮 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 2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}pyrazolo[1,5-a]pyridine
  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

• Indolizines and aza-analog derivatives thereof as CNS active compounds
  申请人：SCHWARZ PHARMA AG

  公开号：EP1972628A1

  公开（公告）日：2008-09-24

  Presently disclosed are indolicine-based compounds of the general formula which have medical utility, for example as antipsychotics.

  目前披露的是具有医疗用途的通式为的基于吲哚啉的化合物，例如作为抗精神病药物。
• INDOLIZINES AND AZA-ANALOG DERIVATIVES THEREOF AS CNS ACTIVE COMPOUNDS
  申请人：Gmeiner Peter

  公开号：US20100168125A1

  公开（公告）日：2010-07-01

  The present application relates to indolizine-based compounds of the general formula (I) and aza-analogs thereof, which have medical utility, for example as antipsychotics.

  本申请涉及基于吲哚嗪的化合物的一般式(I)和其氮杂环类似物，这些化合物具有医学效用，例如作为抗精神病药物。
• [EN] INDOLIZINES AND AZA-ANALOG DERIVATIVES THEREOF AS CNS ACTIVE COMPOUNDS<br/>[FR] INDOLIZINES ET DÉRIVÉS ANALOGUES AZA DE CELLES-CI EN TANT QUE COMPOSÉS ACTIFS SUR LE SYSTÈME NERVEUX CENTRAL
  申请人：SANOL ARZNEI SCHWARZ GMBH

  公开号：WO2008113559A2

  公开（公告）日：2008-09-25

  [EN] The present application relates to indolizine-based compounds of the general formula (I) and aza-analogs thereof, which have medical utility, for example as antipsychotics.
  [FR] La présente invention porte sur des composés à base d'indolizine de la formule générale (I) et sur les analogues aza de ceux-ci, qui ont une utilité médicale, par exemple comme antipsychotiques.
• 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.