4-[4-[[(2R)-2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide | 1174130-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[4-[[(2R)-2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide
• 英文别名: (R)-3-fluoro-4-[4-[2-(3,5-dimethylphenyl)pyrrolidin-1-yl-methyl]phenoxy]benzamide；CERC-501(LY-2456302,Aticaprant)
• CAS: 1174130-62-1
• 化学式: C₂₆H₂₇FN₂O₂
• 分子量: 418.511
• InChiKey: ZHPMYDSXGRRERG-XMMPIXPASA-N

物化性质

• 沸点：
  519.2±50.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氟苯腈 在 双氧水 、 potassium carbonate 作用下， 以 甲醇 、 二甲基十二/十四烷基叔胺 、 乙醇 、 正庚烷 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-[4-[[(2R)-2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide
  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

文献信息

• KAPPA SELECTIVE OPIOID RECEPTOR ANTAGONIST
  申请人：Buezo Nuria Diaz

  公开号：US20090186873A1

  公开（公告）日：2009-07-23

  A selective kappa opioid receptor antagonist useful for treating ethanol use disorder withdrawal and anxiety, and/or depression, or schizophrenia as independent comorbid conditions.

  一种选择性kappa阿片受体拮抗剂，可用于治疗乙醇使用障碍的戒断症状、焦虑症、抑郁症，或作为独立的并发症治疗精神分裂症。
• US7709522B2
  申请人：——

  公开号：US7709522B2

  公开（公告）日：2010-05-04
• US8173695B2
  申请人：——

  公开号：US8173695B2

  公开（公告）日：2012-05-08
• [EN] KAPPA SELECTIVE OPIOID RECEPTOR ANTAGONIST<br/>[FR] ANTAGONISTE SÉLECTIF DES RÉCEPTEURS D'OPIOÏDES KAPPA
  申请人：LILLY CO ELI

  公开号：WO2009094260A1

  公开（公告）日：2009-07-30

  A selective kappa opioid receptor antagonist having the Formula (I) useful for treating ethanol use disorder withdrawal and anxiety, and/or depression, or schizophrenia as independent comorbid conditions.