1-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(2-oxo-1,2-dihydroquinolin-8-yl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(2-oxo-1,2-dihydroquinolin-8-yl)urea
• 英文别名: 1-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]methyl]-3-(2-oxo-1H-quinolin-8-yl)urea
• 化学式: C₂₃H₂₄F₃N₅O₂
• 分子量: 459.471
• InChiKey: WUPFTVXEMIKVBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  86.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  8-硝基-1H-喹啉-2-酮 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 1-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(2-oxo-1,2-dihydroquinolin-8-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

• Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift
  作者：Shivaji A. Thorat、Yoonji Lee、Aeran Jung、Jihyae Ann、Songyeon Ahn、Jisoo Baek、Dongxu Zuo、Nayeon Do、Jin Ju Jeong、Peter M. Blumberg、Timothy E. Esch、Noe A. Turcios、Larry V. Pearce、Hee-Jin Ha、Young Dong Yoo、Sunhye Hong、Sun Choi、Jeewoo Lee

  DOI：10.1021/acs.jmedchem.0c00982

  日期：2021.1.14

  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.