5-(3-甲氧基苯基)-1-(4-三氟甲基苯基)吡咯烷-2,3-二酮 | 1059188-77-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 5-(3-甲氧基苯基)-1-(4-三氟甲基苯基)吡咯烷-2,3-二酮
• 英文名称: 5-(3-methoxyphenyl)-1-(4-trifluoromethylphenyl)pyrrolidine-2,3-dione
• 英文别名: 5-(3-Methoxyphenyl)-1-[4-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione
• CAS: 1059188-77-0
• 化学式: C₁₈H₁₄F₃NO₃
• 分子量: 349.309
• InChiKey: JKCOETRUCBWBBE-UHFFFAOYSA-N

物化性质

• 熔点：
  134-144 °C
• 沸点：
  453.5±55.0 °C(Predicted)
• 密度：
  1.350±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(3-甲氧基苯基)-1-(4-三氟甲基苯基)吡咯烷-2,3-二酮 以17的产率得到(R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)-1,5-dihydropyrrol-2-one
  参考文献：
  名称：

  J. Med. Chem. 2008, 51, 5833-5842

  摘要：

  DOI：
• 作为产物：
  描述：

  5-(3-甲氧基苯基)-1-(4-三氟甲基苯基)-3-(4-三氟甲基苯基氨基)-1,5-二氢吡咯-2-酮 在 盐酸 、 水 、 溶剂黄146 作用下， 反应 45.0h， 以80%的产率得到5-(3-甲氧基苯基)-1-(4-三氟甲基苯基)吡咯烷-2,3-二酮
  参考文献：
  名称：

  Synthesis, Ex Vivo Evaluation, and Radiolabeling of Potent 1,5-Diphenylpyrrolidin-2-one Cannabinoid Subtype-1 Receptor Ligands as Candidates for In Vivo Imaging

  摘要：

  We have reported that [methyl-C-11] (3R,5R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([C-11]8, [C-11]MePPEP) binds with high selectivity to cannabinoid type-l (CB1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely, the 4-fluorophenyl (16, FMePPEP), 3-fluoromethoxy (20, FMPEP), 3-fluoromethoxy-d(2) (21, FMPEP-d(2)), and 3-fluoroethoxy analogues (22, FEPEP), and report their activity in an ex vivo model designed to identify compounds suitable for use as positron emission tomography (PET) ligands. These ligands exhibited high, selective potency at CB I receptors in vitro (K-b < 1 nM). Each ligand (30 mu g/kg, iv) was injected into rats under baseline and pretreatment conditions (3, rimonabant, 10 mg/kg, iv) and quantified at later times in frontal cortex ex vivo with liquid chromatography-mass spectrometry (LC-MS) detection. Maximal ligand uptakes were high (22.6-48.0 ng/g). Under pretreatment, maximal brain uptakes were greatly reduced (6.5 - 17.3 ng/g). Since each ligand readily entered brain and bound with high selectivity to CB 1 receptors, we then established and here describe methods for producing [C-11]8, [C-11] 16, and [[F-18]20-22 in adequate activities for evaluation as candidate PET radioligands in vivo.

  DOI：

  10.1021/jm800416m

文献信息

• 1,5-DIPHENYL-PYRROLIDIN-2-ONE COMPOUNDS AS CB-1 LIGANDS
  申请人：Hu Jingdan

  公开号：US20110028520A1

  公开（公告）日：2011-02-03

  CB-1 receptor inverse agonist compounds of Formula and pharmaceutical compositions for the treatment of obesity or cognitive impairment associated with schizophrenia.

  公式为CB-1受体反向激动剂化合物和制药组合物，用于治疗肥胖症或与精神分裂症相关的认知障碍。
• US8426448B2
  申请人：——

  公开号：US8426448B2

  公开（公告）日：2013-04-23
• [EN] 1,5-DIPHENYL-PYRROLIDIN-2-ONE COMPOUNDS AS CB-1 LIGANDS<br/>[FR] COMPOSÉS DE 1,5-DIPHÉNYL-PYRROLIDIN-2-ONE COMME LIGANDS DE CB-1
  申请人：LILLY CO ELI

  公开号：WO2009131814A2

  公开（公告）日：2009-10-29

  CB-1 receptor inverse agonist compounds of Formula and pharmaceutical compositions for the treatment of obesity or cognitive impairment associated with schizophrenia.
• Synthesis, Ex Vivo Evaluation, and Radiolabeling of Potent 1,5-Diphenylpyrrolidin-2-one Cannabinoid Subtype-1 Receptor Ligands as Candidates for In Vivo Imaging
  作者：Sean R. Donohue、Joseph H. Krushinski、Victor W. Pike、Eyassu Chernet、Lee Phebus、Amy K. Chesterfield、Christian C. Felder、Christer Halldin、John M. Schaus

  DOI：10.1021/jm800416m

  日期：2008.9.25

  We have reported that [methyl-C-11] (3R,5R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([C-11]8, [C-11]MePPEP) binds with high selectivity to cannabinoid type-l (CB1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely, the 4-fluorophenyl (16, FMePPEP), 3-fluoromethoxy (20, FMPEP), 3-fluoromethoxy-d(2) (21, FMPEP-d(2)), and 3-fluoroethoxy analogues (22, FEPEP), and report their activity in an ex vivo model designed to identify compounds suitable for use as positron emission tomography (PET) ligands. These ligands exhibited high, selective potency at CB I receptors in vitro (K-b < 1 nM). Each ligand (30 mu g/kg, iv) was injected into rats under baseline and pretreatment conditions (3, rimonabant, 10 mg/kg, iv) and quantified at later times in frontal cortex ex vivo with liquid chromatography-mass spectrometry (LC-MS) detection. Maximal ligand uptakes were high (22.6-48.0 ng/g). Under pretreatment, maximal brain uptakes were greatly reduced (6.5 - 17.3 ng/g). Since each ligand readily entered brain and bound with high selectivity to CB 1 receptors, we then established and here describe methods for producing [C-11]8, [C-11] 16, and [[F-18]20-22 in adequate activities for evaluation as candidate PET radioligands in vivo.
• J. Med. Chem. 2008, 51, 5833-5842
  作者：

  DOI：——

  日期：——