5-amino-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine | 866216-20-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-amino-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine
• 英文别名: 4,5,6,7-Tetrahydropyrazolo[1,5-a]pyridin-5-amine
• CAS: 866216-20-8
• 化学式: C₇H₁₁N₃
• mdl: MFCD13176247
• 分子量: 137.184
• InChiKey: JJNXSQRHVCZLAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-amino-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine 在 三乙酰氧基硼氢化钠 、 sodium cyanoborohydride 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 18.75h， 生成 N-(4-(4-phenylbenzoylamino)butyl)-N-propyl-5-amino-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D₃ Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions

  摘要：

  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.

  DOI：

  10.1021/jm101639t
• 作为产物：
  描述：

  1H-pyrazolo[1,5-a]pyridin-5-one 在 palladium on activated charcoal sodium azide 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， -30.0~80.0 ℃ 、2.0 MPa 条件下， 反应 43.5h， 生成 5-amino-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  药理学指导的药物发现研究，导致生物活性的5-氨基四氢吡唑并吡啶。对杂环多巴胺D3受体激动剂的结合方式的影响。

  摘要：

  利用基于3D-QSAR的药效团假说，描述了多巴胺能5-氨基四氢吡唑并[1,5-a]吡啶的合成和生物学评估。当对映异构体（S）-1证明是与D3结合的原因时，数据显示出对杂环测试化合物（+/-）-1的实质性和选择性D3受体亲和力（K（i）（高）= 4.0 nM） 。（S）-1表现出与我们先前描述的D3激动剂FAUC 54相当的结合亲和力和配体功效，可显着改善亚型的选择性。结果表明，多巴胺能药物（S）-1和普拉克索的吡唑和噻唑环的sp（2）氮分别是最重要的药效学元素。为了提供对（S）-1的高亲和力的推定解释，

  DOI：

  10.1021/jm0503805

文献信息

• [EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS POUR LA RESTAURATION DE LA FONCTION DU P53 MUTANT
  申请人：PMV PHARMACEUTICALS INC

  公开号：WO2021231474A9

  公开（公告）日：2022-01-13
• Pharmacophore-Guided Drug Discovery Investigations Leading to Bioactive 5-Aminotetrahydropyrazolopyridines. Implications for the Binding Mode of Heterocyclic Dopamine D3 Receptor Agonists
  作者：Jan Elsner、Frank Boeckler、Frank W. Heinemann、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm0503805

  日期：2005.9.1

  advantage of a 3D-QSAR based pharmacophore hypothesis, synthesis and biological evaluation of dopaminergic 5-aminotetrahydropyrazolo[1,5-a]pyridines are described. The data displayed substantial and selective D3 receptor affinity for the heterocyclic test compound (+/-)-1 when the enantiomer (S)-1 turned out to be responsible for the D3 binding (K(i) (high) = 4.0 nM). (S)-1 exhibited binding affinity

  利用基于3D-QSAR的药效团假说，描述了多巴胺能5-氨基四氢吡唑并[1,5-a]吡啶的合成和生物学评估。当对映异构体（S）-1证明是与D3结合的原因时，数据显示出对杂环测试化合物（+/-）-1的实质性和选择性D3受体亲和力（K（i）（高）= 4.0 nM） 。（S）-1表现出与我们先前描述的D3激动剂FAUC 54相当的结合亲和力和配体功效，可显着改善亚型的选择性。结果表明，多巴胺能药物（S）-1和普拉克索的吡唑和噻唑环的sp（2）氮分别是最重要的药效学元素。为了提供对（S）-1的高亲和力的推定解释，
• 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.