1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide | 1015765-20-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide
• 英文别名: 1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-yl-5-pyrrol-1-ylpyrazole-3-carboxamide
• CAS: 1015765-20-4
• 化学式: C₂₀H₂₁Cl₂N₅O
• 分子量: 418.326
• InChiKey: JYMFGFSCTSBMDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(2,4-二氯苯基)-4-甲基-5-(1H-吡咯-1-y)-1H-吡唑-3-羧酸 、 1-氨基哌啶 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  探索第一个Rimonabant类似物-阿片肽杂合化合物，作为CB1和阿片受体的二价配体。

  摘要：

  大麻素（CB）和阿片类药物系统均与镇痛，食物摄入，情绪和行为有关。由于在中枢神经系统（CNS）的各个区域中，μ阿片类药物（MOR）和CB1受体共定位，并且它们具有形成异二聚体的能力，因此针对这两个系统的二价配体可能是研究是否存在阿片类药物的良好候选者。在次有效剂量下也可能产生串扰或协同效应。在这项工作中，我们从一小部分新的Rimonabant类似物中选择一种CB1R反向激动剂与阿片样物质Tyr-D-Ala-Gly-Phe-NH2偶联。二价化合物（9）已用于体外结合测定，体内抗伤害感受模型和体外下丘脑灌注试验，以评估神经递质的释放。

  DOI：

  10.1080/14756366.2016.1260565

文献信息

• Synthesis, Cannabinoid Receptor Affinity, and Molecular Modeling Studies of Substituted 1-Aryl-5-(1<i>H</i>-pyrrol-1-yl)-1<i>H</i>-pyrazole-3-carboxamides
  作者：Romano Silvestri、Maria Grazia Cascio、Giuseppe La Regina、Francesco Piscitelli、Antonio Lavecchia、Antonella Brizzi、Serena Pasquini、Maurizio Botta、Ettore Novellino、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm070566z

  日期：2008.3.1

  The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB(1) and hCB(2) receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB(1). On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound 26 was the most selective ligand for the hCB(1) receptor (K-i (CB2)/K-i (CB1) = 140.7). Derivative 30, the most potent hCB(1) ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 similar to 1 nM). The carbonyl oxygen of both 26 and 30 formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors' inactive state and the inverse agonist activity.
• Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors
  作者：Adriano Mollica、Sveva Pelliccia、Valeria Famiglini、Azzurra Stefanucci、Giorgia Macedonio、Annalisa Chiavaroli、Giustino Orlando、Luigi Brunetti、Claudio Ferrante、Stefano Pieretti、Ettore Novellino、Sandor Benyhe、Ferenc Zador、Anna Erdei、Edina Szucs、Reza Samavati、Szabolcs Dvorácskó、Csaba Tomboly、Rino Ragno、Alexandros Patsilinakos、Romano Silvestri

  DOI：10.1080/14756366.2016.1260565

  日期：2017.1.1

  Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects

  大麻素（CB）和阿片类药物系统均与镇痛，食物摄入，情绪和行为有关。由于在中枢神经系统（CNS）的各个区域中，μ阿片类药物（MOR）和CB1受体共定位，并且它们具有形成异二聚体的能力，因此针对这两个系统的二价配体可能是研究是否存在阿片类药物的良好候选者。在次有效剂量下也可能产生串扰或协同效应。在这项工作中，我们从一小部分新的Rimonabant类似物中选择一种CB1R反向激动剂与阿片样物质Tyr-D-Ala-Gly-Phe-NH2偶联。二价化合物（9）已用于体外结合测定，体内抗伤害感受模型和体外下丘脑灌注试验，以评估神经递质的释放。