4-[4-[[2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide | 1174130-60-9

• 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-[[2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide
• 英文别名: (±)LY2456302；LY2456302；4-{4-[2-(3,5-dimethyl-phenyl)-pyrrolidin-1-ylmethyl]-phenoxy}-3-fluoro-benzamide；4-(4-((2-(3,5-Dimethylphenyl)pyrrolidin-1-yl)methyl)phenoxy)-3-fluorobenzamide
• CAS: 1174130-60-9
• 化学式: C₂₆H₂₇FN₂O₂
• 分子量: 418.511
• InChiKey: ZHPMYDSXGRRERG-UHFFFAOYSA-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

• 作为反应物：
  描述：

  4-[4-[[2-(3,5-dimethylphenyl)pyrrolidin-1-yl]methyl]phenoxy]-3-fluorobenzamide 以24的产率得到(S)-4-(4-((2-(3,5-二甲基苯基)吡咯烷-1-基)甲基)苯氧基)-3-氟苯甲酰胺
  参考文献：
  名称：

  KAPPA SELECTIVE OPIOID RECEPTOR ANTAGONIST

  摘要：

  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条件的精神分裂症。

  公开号：

  US20100197669A1
• 作为产物：
  描述：

  对羟基苯甲醛 在 双氧水 、 potassium carbonate 作用下， 以 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-[[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

• Use of an opioid receptor antagonist with kappa-activity and vortioxetine for treatment of depressive disorder with melancholic features
  申请人：H. Lundbeck A/S

  公开号：US10376506B2

  公开（公告）日：2019-08-13

  The present invention relates to an opioid antagonist with κ-activity for use in treatment of depressive disorder with melancholic features. The invention further relates to the combination of an opioid antagonist with κ-activity and vortioxetine for use in treatment of depressive disorder with melancholic features. The invention also relates to pharmaceutical compositions comprising an opioid antagonist with κ-activity and vortioxetine.

  本发明涉及一种具有κ活性的阿片拮抗剂，用于治疗具有忧郁特征的抑郁障碍。本发明进一步涉及一种具有κ活性的阿片拮抗剂与伏替西汀的组合，用于治疗具有忧郁特征的抑郁障碍。本发明还涉及由具有κ活性的阿片拮抗剂和伏替西汀组成的药物组合物。
• USE OF AN OPIOID RECEPTOR ANTAGONIST WITH KAPPA-ACTIVITY AND VORTIOXETINE FOR TREATMENT OF DEPRESSIVE DISORDER WITH MELANCHOLIC FEATURES
  申请人：H. Lundbeck A/S

  公开号：EP3082815A1

  公开（公告）日：2016-10-26
• JP2011524850A
  申请人：——

  公开号：JP2011524850A

  公开（公告）日：2011-09-08
• JP5345637B2
  申请人：——

  公开号：JP5345637B2

  公开（公告）日：2013-11-20
• Use of an Opioid Receptor Antagonist with Kappa-Activity and Vortioxetine for Treatment of Depressive Disorder with Melancholic Features
  申请人：H. LUNDBECK A/S

  公开号：US20160310488A1

  公开（公告）日：2016-10-27

  The present invention relates to an opioid antagonist with κ-activity for use in treatment of depressive disorder with melancholic features. The invention further relates to the combination of an opioid antagonist with κ-activity and vortioxetine for use in treatment of depressive disorder with melancholic features. The invention also relates to pharmaceutical compositions comprising an opioid antagonist with κ-activity and vortioxetine.