6-[4-[[ (3-hydroxy-2,2-dimethyl-1-phenyl-propyl)amino]methyl]phenoxy]pyridine-3-carboxamide | 1346133-14-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-[4-[[ (3-hydroxy-2,2-dimethyl-1-phenyl-propyl)amino]methyl]phenoxy]pyridine-3-carboxamide
• 英文别名: 6-[4-[[(3-Hydroxy-2,2-dimethyl-1-phenylpropyl)amino]methyl]phenoxy]pyridine-3-carboxamide
• CAS: 1346133-14-9
• 化学式: C₂₄H₂₇N₃O₃
• 分子量: 405.497
• InChiKey: CFEJZXBLGIJYMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  97.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-[4-[[ (3-hydroxy-2,2-dimethyl-1-phenyl-propyl)amino]methyl]phenoxy]pyridine-3-carboxamide 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 以74%的产率得到6-[4-[ (3,3-dimethyl-2-phenyl-azetidin-1-yl)methyl]phenoxy]pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer

  摘要：

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.

  DOI：

  10.1021/jm200789r
• 作为产物：
  描述：

  6-氟-烟腈 在 双氧水 、 potassium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-[4-[[ (3-hydroxy-2,2-dimethyl-1-phenyl-propyl)amino]methyl]phenoxy]pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer

  摘要：

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.

  DOI：

  10.1021/jm200789r