N-(4-hydroxybutyl)pyrazolo[1,5-a]pyridine-2-carboxamide | 1443762-39-7

• 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: N-(4-hydroxybutyl)pyrazolo[1,5-a]pyridine-2-carboxamide
• CAS: 1443762-39-7
• 化学式: C₁₂H₁₅N₃O₂
• 分子量: 233.27
• InChiKey: VYSUAEVRNKVABF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxybutyl)pyrazolo[1,5-a]pyridine-2-carboxamide 、 4-ethynyl-N-propylcyclohex-3-enamine 在 三氧化硫吡啶 、 三乙胺 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.0h， 以12%的产率得到(R)-N-[4-[(4-ethynylcyclohex-3-enyl)propylamino]butyl]-pyrazolo[1,5-a]pyridine-2-carboxamide
  参考文献：
  名称：

  Functionally Selective Dopamine D₂/D₃ Receptor Agonists Comprising an Enyne Moiety

  摘要：

  Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-2-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D-2L- and D-2S-mediated [S-35]GTP gamma S incorporation in the presence of coexpressed G alpha(o) and G alpha(i) subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-2S-promoted G(o) activation over G(i) coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G(o) activation than for G, coupling at the D-2L subtype. Functional selectivity for beta-arrestin recruitment over G(i) activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred beta-arrestin recruitment compared to G(o) coupling.

  DOI：

  10.1021/jm400520c
• 作为产物：
  描述：

  4-氨基-1-丁醇 、 吡唑并[1,5-a]吡啶-2-甲酸 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以75%的产率得到N-(4-hydroxybutyl)pyrazolo[1,5-a]pyridine-2-carboxamide
  参考文献：
  名称：

  Functionally Selective Dopamine D₂/D₃ Receptor Agonists Comprising an Enyne Moiety

  摘要：

  Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-2-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D-2L- and D-2S-mediated [S-35]GTP gamma S incorporation in the presence of coexpressed G alpha(o) and G alpha(i) subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-2S-promoted G(o) activation over G(i) coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G(o) activation than for G, coupling at the D-2L subtype. Functional selectivity for beta-arrestin recruitment over G(i) activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred beta-arrestin recruitment compared to G(o) coupling.

  DOI：

  10.1021/jm400520c

文献信息

• Functionally Selective Dopamine D₂/D₃ Receptor Agonists Comprising an Enyne Moiety
  作者：Christine Hiller、Ralf C. Kling、Frank W. Heinemann、Karsten Meyer、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm400520c

  日期：2013.6.27

  Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-2-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D-2L- and D-2S-mediated [S-35]GTP gamma S incorporation in the presence of coexpressed G alpha(o) and G alpha(i) subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-2S-promoted G(o) activation over G(i) coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G(o) activation than for G, coupling at the D-2L subtype. Functional selectivity for beta-arrestin recruitment over G(i) activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred beta-arrestin recruitment compared to G(o) coupling.