pyrazolo[1,5-a]pyridin-6-ylmethanol | 362661-88-9

• 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: pyrazolo[1,5-a]pyridin-6-ylmethanol
• CAS: 362661-88-9
• 化学式: C₈H₈N₂O
• 分子量: 148.164
• InChiKey: NJOUFCWSJNYISL-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  pyrazolo[1,5-a]pyridin-6-ylmethanol 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 6-[4-(4-Chloro-phenyl)-piperazin-1-ylmethyl]-pyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  Rationally Based Efficacy Tuning of Selective Dopamine D4 Receptor Ligands Leading to the Complete Antagonist 2-[4-(4-Chlorophenyl)piperazin-1- ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 213)

  摘要：

  Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the intrinsic activity of the regioisomers investigated is controlled by the ability of the heterocyclic unit to interact with both elements of the D4 binding-site crevice, the aromatic microdomain in TM6, and a serine residue in TM5.

  DOI：

  10.1021/jm015522j
• 作为产物：
  描述：

  N-amino-3-(hydroxymethyl)pyridinium mesityl sulfonate 在 硫酸 、 氧气 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 pyrazolo[1,5-a]pyridin-6-ylmethanol
  参考文献：
  名称：

  Rationally Based Efficacy Tuning of Selective Dopamine D4 Receptor Ligands Leading to the Complete Antagonist 2-[4-(4-Chlorophenyl)piperazin-1- ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 213)

  摘要：

  Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the intrinsic activity of the regioisomers investigated is controlled by the ability of the heterocyclic unit to interact with both elements of the D4 binding-site crevice, the aromatic microdomain in TM6, and a serine residue in TM5.

  DOI：

  10.1021/jm015522j

文献信息

• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES ASSOCIÉES POUR LE TRAITEMENT DE MALADIES
  申请人：GALAPAGOS NV

  公开号：WO2020239658A1

  公开（公告）日：2020-12-03

  The present invention discloses compounds according to Formula (I), wherein R1a, R1b, R1c, R2a, W1, W2, X1, X2, X3, Y, and Z are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of inflammatory diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, fibrotic diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformation, diseases involving impairment of bone turnover, diseases associated with hypersecretion of IL-6, diseases associated with hypersecretion of TNFα, interferons, IL-12 and/or IL-23, respiratory diseases, endocrine and/or metabolic diseases, cardiovascular diseases, dermatological diseases, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1a、R1b、R1c、R2a、W1、W2、X1、X2、X3、Y和Z如本文所定义。本发明涉及化合物、其生产方法、包括其在内的制药组合物，以及使用这些化合物进行预防和/或治疗炎症性疾病、自身炎症性疾病、自身免疫性疾病、增生性疾病、纤维化疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形、涉及骨周转障碍的疾病、与IL-6过度分泌有关的疾病、与TNFα、干扰素、IL-12和/或IL-23过度分泌有关的疾病、呼吸系统疾病、内分泌和/或代谢性疾病、心血管疾病、皮肤病和/或异常血管生成相关疾病的治疗方法，通过给予本发明的化合物。
• Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine receptor binding and ligand efficacy
  作者：Stefan Löber、Tarek Aboul-Fadl、Harald Hübner、Peter Gmeiner

  DOI：10.1016/s0960-894x(01)00814-9

  日期：2002.2

  Based on the lead molecule FAUC 113, a series of di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed excellent pharmacological properties combining high D4 affinity (K-i = 1.5 nM) and selectivity with significant intrinsic activity (31%) in low nanomolar concentrations (EC50 = 1.5 nM), (C) 2002 Elsevier Science Ltd. All rights reserved.
• NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES
  申请人：Galapagos N.V.

  公开号：EP3976189A1

  公开（公告）日：2022-04-06
• GPR17 MODULATORS AND USES THEREOF
  申请人：[en]MYROBALAN THERAPEUTICS NANJING CO. LTD

  公开号：WO2024104462A1

  公开（公告）日：2024-05-23

  Disclosed herein are compounds capable of modulating GPR17 and pharmaceutical compositions of such compounds and methods of treatment for conditions, e.g., neurodegenerative diseases or demyelinating diseases, using such pharmaceutical compositions.
• Rationally Based Efficacy Tuning of Selective Dopamine D4 Receptor Ligands Leading to the Complete Antagonist 2-[4-(4-Chlorophenyl)piperazin-1- ylmethyl]pyrazolo[1,5-<i>a</i>]pyridine (FAUC 213)
  作者：Stefan Löber、Harald Hübner、Wolfgang Utz、Peter Gmeiner

  DOI：10.1021/jm015522j

  日期：2001.8.1

  Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the intrinsic activity of the regioisomers investigated is controlled by the ability of the heterocyclic unit to interact with both elements of the D4 binding-site crevice, the aromatic microdomain in TM6, and a serine residue in TM5.