1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(1-oxo-1,2-dihydroisoquinolin-5-yl)urea | 1254713-09-1

• 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-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(1-oxo-1,2-dihydroisoquinolin-5-yl)urea
• 英文别名: 1-[[2-(3-chlorophenyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]-3-(1-oxo-2H-isoquinolin-5-yl)urea
• CAS: 1254713-09-1
• 化学式: C₂₁H₁₅ClF₃N₅O₂
• 分子量: 461.831
• InChiKey: IMADJLCKZYXRAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  88
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-氨基-1(2H)-异喹啉酮 在 吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(1-oxo-1,2-dihydroisoquinolin-5-yl)urea
  参考文献：
  名称：

  Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift

  摘要：

  Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and potent antagonism, whereas 1-oxo-1,2-dihydroisoquinolin-5-yl analogues (e.g., 3) showed full agonism with high potency. Our computational models provide insight into the agonist-antagonist boundary of the analogues suggesting that the Arg557 residue in the S4-S5 linker might be important for sensing the agonist binding and transmitting signals. These results provide structural insights into the TRPV1 and the protein-ligand interactions at a molecular level.

  DOI：

  10.1021/acs.jmedchem.0c00982

文献信息

• [EN] SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE AROMATIQUE ET D'URÉE SUBSTITUÉS EN TANT QUE LIGANDS DU RÉCEPTEUR VANILLOÏDE
  申请人：GRUENENTHAL GMBH

  公开号：WO2010127855A1

  公开（公告）日：2010-11-11

  The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).

  这项发明涉及取代芳香族羧酰胺和脲衍生物，以及其制备方法，含有这些化合物的药物组合物，以及利用这些化合物制备药物组合物的用途（式（I））。
• Substituted Aromatic Carboxamide and Urea Derivatives as Vanilloid Receptor Ligands
  申请人：FRANK Robert

  公开号：US20110003795A1

  公开（公告）日：2011-01-06

  The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions.

  该发明涉及取代芳香族羧酰胺和脲衍生物，其制备过程，含有这些化合物的药物组合物以及利用这些化合物制备药物组合物的用途。
• SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
  申请人：Grünenthal GmbH

  公开号：EP2427436A1

  公开（公告）日：2012-03-14
• US8334315B2
  申请人：——

  公开号：US8334315B2

  公开（公告）日：2012-12-18