吡唑并[1,5-a]吡啶-4-甲醛 | 474432-58-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 中文名称: 吡唑并[1,5-a]吡啶-4-甲醛
• 英文名称: (pyrazolo[1,5-a]pyridin-4-yl)methanone
• 英文别名: pyrazolo[1,5-a]pyridine-4-carbaldehyde；pyrazolo[1,5-a]pyridinal
• CAS: 474432-58-1
• 化学式: C₈H₆N₂O
• mdl: MFCD12828628
• 分子量: 146.148
• InChiKey: OYEYGVCZFMWJMV-UHFFFAOYSA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  吡唑并[1,5-a]吡啶-4-甲醛 在 manganese(IV) oxide 、 sodium hydroxide 、 氰化钠 、 溶剂黄146 作用下， 反应 4.0h， 生成 吡唑并[1,5-a]吡啶-4-羧酸
  参考文献：
  名称：

  交互式SAR研究：合理发现超强效和高度选择性的多巴胺D3受体拮抗剂和部分激动剂。

  摘要：

  从多巴胺受体配体BP897开始，证明了导致杂环生物等排体的交互式药物发现过程。四步策略涉及分别通过系统地修饰连接点和杂原子来仔细优化几何和电子性质。通过修饰苯基取代基来调节功效可导致D3部分激动剂和完全拮抗剂。苯并噻吩3c（FAUC346）和3d（FAUC365）显示出出色的D3亲和力和亚型选择性。

  DOI：

  10.1021/jm025558r

文献信息

• 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
  申请人：H. Lundbeck A/S

  公开号：US20190194189A1

  公开（公告）日：2019-06-27

  The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

  本发明提供了式(I)的1H-吡唑并[4,3-b]吡啶类化合物作为PDE1抑制剂，并将其用作药物，特别用于治疗神经退行性疾病和精神疾病。
• Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington’s Disease
  作者：Tammy Ladduwahetty、Matthew R. Lee、Michel C. Maillard、Roger Cachope、Daniel Todd、Michael Barnes、Vahri Beaumont、Alka Chauhan、Caroline Gallati、Alan F. Haughan、Georg Kempf、Christopher A. Luckhurst、Kim Matthews、George McAllister、Philip Mitchell、Hiral Patel、Mark Rose、Elizabeth Saville-Stones、Stefan Steinbacher、Andrew J. Stott、Emma Thatcher、Jason Tierney、Liudvikas Urbonas、Ignacio Munoz-Sanjuan、Celia Dominguez

  DOI：10.1021/acs.jmedchem.2c00474

  日期：2022.7.28

  nervous system (CNS)-penetrant ROCK inhibitor. Identifying a compound that could be dosed orally in mice with selectivity against other AGC kinases, including protein kinase G (PKG), whose inhibition could potentially activate the ROCK pathway, was paramount for the program. We describe the optimization of published ligands to identify a novel series of ROCK inhibitors based on a piperazine core. Morphing

  Rho 激酶 (ROCK) 通路涉及多种疾病的发病机制，包括神经系统疾病。在亨廷顿病 (HD) 中，ROCK 与突变亨廷顿 (HTT) 聚集和神经毒性有关，并且 ROCK 通路的成员在 HD 小鼠模型和患者中增加。为了验证这种作用模式作为 HD 的潜在治疗方法，我们寻求一种有效的、选择性的、中枢神经系统 (CNS) 渗透性 ROCK 抑制剂。确定一种可以在小鼠中口服给药的化合物，该化合物对其他 AGC 激酶具有选择性，包​​括蛋白激酶 G (PKG)，其抑制作用可能会激活 ROCK 通路，对于该计划至关重要。我们描述了已发表的配体的优化，以识别基于哌嗪核心的一系列新型 ROCK 抑制剂。
• 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
  申请人：H. Lundbeck A/S

  公开号：US10766893B2

  公开（公告）日：2020-09-08

  The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

  本发明提供了作为 PDE1 抑制剂的式 (I) 的 1H-吡唑并[4,3-b]吡啶及其作为药物的用途，特别是用于治疗神经退行性疾病和精神疾病。
• Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D₃ Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions
  作者：Nuska Tschammer、Jan Elsner、Angela Goetz、Katharina Ehrlich、Stefan Schuster、Miriam Ruberg、Julia Kühhorn、Dawn Thompson、Jennifer Whistler、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm101639t

  日期：2011.4.14

  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.
• 1H -PYRAZOLO[4,3-b ]PYRIDINES AS PDE1 INHIBITORS
  申请人：H. Lundbeck A/S

  公开号：EP3728249A1

  公开（公告）日：2020-10-28