dimethyl 5-methoxypyrazolo[1,5-a]pyridine-2,3-dicarboxylate | 1610742-50-1

• 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: dimethyl 5-methoxypyrazolo[1,5-a]pyridine-2,3-dicarboxylate
• CAS: 1610742-50-1
• 化学式: C₁₂H₁₂N₂O₅
• 分子量: 264.238
• InChiKey: YASVSMYZXOXMBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  79.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-amino-4-methoxypyridinium 2,4-dinitrophenolate 、 丁炔二酸二甲酯 在 potassium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以23%的产率得到dimethyl 5-methoxypyrazolo[1,5-a]pyridine-2,3-dicarboxylate
  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

• New approach toward the synthesis of deuterated pyrazolo[1,5-<i>a</i>]pyridines and 1,2,4-triazolo[1,5-<i>a</i>]pyridines
  作者：Aleksey Yu Vorob’ev、Vyacheslav I Supranovich、Gennady I Borodkin、Vyacheslav G Shubin

  DOI：10.3762/bjoc.13.80

  日期：——

  An efficient and operationally simple synthesis of 7-deuteropyrazolo[1,5-a]pyridine and 7-deutero-1,2,4-triazolo[1,5-a]pyridine derivatives using α-H/D exchange of 1-aminopyridinium cations in basic D2O followed by a 1,3-cycloaddition of acetylenes and nitriles is presented. A high regioselectivity and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium

  使用1-氨基吡啶的α-H/ D交换高效有效地合成7-氘代吡唑并[1,5-a]吡啶和7-氘代1,2,4-三唑并[1,5-a]吡啶衍生物提出了碱性D2O中的阳离子，然后进行乙炔和腈的1,3-环加成反应。实现了高区域选择性和高氘结合度。该程序应用于几种4-R-1-氨基吡啶鎓阳离子（R = H，Me，OMe）。
• [EN] COMPOUND AS WNT SIGNAL PATHWAY INHIBITOR AND MEDICAL USE THEREOF<br/>[FR] COMPOSÉ EN TANT QU'INHIBITEUR DE LA VOIE DE SIGNALISATION WNT ET SON UTILISATION MÉDICALE<br/>[ZH] 作为WNT信号通路抑制剂的化合物及其医学应用
  申请人：HUIHAN MEDICAL TECH LTD CO

  公开号：WO2020125759A1

  公开（公告）日：2020-06-25

  本发明提供了具有WNT信号通路抑制活性的5,6双环结构的化合物和取代5,6杂双环氨基化合物，可以用于WNT信号通路相关疾病的治疗。相关疾病包括但不限于：肿瘤、畸形综合症、骨或软骨疾病、糖尿病或其并发症、组织纤维化等。