methyl trans-3-(5-fluoro-2-methoxyphenyl)propenoate | 175168-69-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl trans-3-(5-fluoro-2-methoxyphenyl)propenoate
• 英文别名: methyl (E)-3-(5-fluoro-2-methoxyphenyl)acrylate；2-Propenoic acid, 3-(5-fluoro-2-methoxyphenyl)-, methyl ester, (E)-；methyl (E)-3-(5-fluoro-2-methoxyphenyl)prop-2-enoate
• CAS: 175168-69-1
• 化学式: C₁₁H₁₁FO₃
• 分子量: 210.205
• InChiKey: JVIYMOIZYNWXKZ-ZZXKWVIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl trans-3-(5-fluoro-2-methoxyphenyl)propenoate 在 palladium diacetate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (1S,2S)-2-(5-fluoro-2-methoxyphenyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  trans-2-Aryl-N,N-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT_1A Receptors

  摘要：

  Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [H-3]-8-OH-DPAT from rat brain 5-HT1A receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7I) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT1A receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT1A receptor affinity. The racemic mixtures of the interesting 7j and 7I were resolved into the enantiomers; 7j and 7I exhibited a high enantiomeric 5-HT1A receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7I were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (LR,2R)-7j behaved as a partial agonist whereas (1R,2S)-7I appeared as an efficacious 5-HT1A receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

  DOI：

  10.1021/jm9507136
• 作为产物：
  描述：

  5-氟-2-甲氧基苯甲醛 、 甲氧羰基亚甲基三苯基正膦 以 二氯甲烷 为溶剂， 以85%的产率得到methyl trans-3-(5-fluoro-2-methoxyphenyl)propenoate
  参考文献：
  名称：

  2-苯基环丙基甲胺衍生物作为多巴胺 D2 受体部分激动剂：设计、合成和生物学评价

  摘要：

  对多巴胺 D 2受体 (D 2 R) 的部分激动剂活性是第三代抗精神病药——阿立哌唑、brexpiprazole 和卡利拉嗪的主要药理学特征。然而，所有这些药物都有一个共同的苯基哌嗪部分作为主要药效团。在这项研究中，我们设计并合成了一系列基于 2-苯基环丙基甲胺 (PCPMA) 支架的新型化合物，并研究了它们在 D 2 R 的药理活性。一些有效的 D 2通过结合亲和力筛选和 G 蛋白和 β-抑制蛋白测定中的功能活性分析鉴定 R 部分激动剂。结构-功能活性关系结果表明，间隔基团对于微调这些化合物的内在活性至关重要。化合物(+)- 14j和(+)- 14l显示出良好的药代动力学特性和对5-羟色胺2A (5-HT 2A ) 受体的出乎意料的选择性。小鼠超运动模型中的初步抑制作用证明这些 PCPMA 衍生的 D 2 R 部分激动剂作为潜在的新型抗精神病药是有效的。

  DOI：

  10.1021/acs.jmedchem.1c01327

文献信息

• <i>trans</i>-2-Aryl-<i>N</i>,<i>N</i>-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT_1A Receptors
  作者：Jerk Vallgårda、Ulf Appelberg、Lars-Erik Arvidsson、Stephan Hjorth、Björn E. Svensson、Uli Hacksell

  DOI：10.1021/jm9507136

  日期：1996.1.1

  Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [H-3]-8-OH-DPAT from rat brain 5-HT1A receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7I) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT1A receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT1A receptor affinity. The racemic mixtures of the interesting 7j and 7I were resolved into the enantiomers; 7j and 7I exhibited a high enantiomeric 5-HT1A receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7I were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (LR,2R)-7j behaved as a partial agonist whereas (1R,2S)-7I appeared as an efficacious 5-HT1A receptor agonist, stimulating both autoreceptors and postsynaptic receptors.
• 2-Phenylcyclopropylmethylamine Derivatives as Dopamine D₂ Receptor Partial Agonists: Design, Synthesis, and Biological Evaluation
  作者：Wenzhong Yan、Luyu Fan、Jing Yu、Ruiquan Liu、Huan Wang、Liang Tan、Sheng Wang、Jianjun Cheng

  DOI：10.1021/acs.jmedchem.1c01327

  日期：2021.12.9

  Partial agonist activity at the dopamine D2 receptor (D2R) is the primary pharmacological feature of the third-generation antipsychotics─aripiprazole, brexpiprazole, and cariprazine. However, all these drugs share a common phenyl-piperazine moiety as the primary pharmacophore. In this study, we designed and synthesized a series of novel compounds based on the 2-phenylcyclopropylmethylamine (PCPMA)

  对多巴胺 D 2受体 (D 2 R) 的部分激动剂活性是第三代抗精神病药——阿立哌唑、brexpiprazole 和卡利拉嗪的主要药理学特征。然而，所有这些药物都有一个共同的苯基哌嗪部分作为主要药效团。在这项研究中，我们设计并合成了一系列基于 2-苯基环丙基甲胺 (PCPMA) 支架的新型化合物，并研究了它们在 D 2 R 的药理活性。一些有效的 D 2通过结合亲和力筛选和 G 蛋白和 β-抑制蛋白测定中的功能活性分析鉴定 R 部分激动剂。结构-功能活性关系结果表明，间隔基团对于微调这些化合物的内在活性至关重要。化合物(+)- 14j和(+)- 14l显示出良好的药代动力学特性和对5-羟色胺2A (5-HT 2A ) 受体的出乎意料的选择性。小鼠超运动模型中的初步抑制作用证明这些 PCPMA 衍生的 D 2 R 部分激动剂作为潜在的新型抗精神病药是有效的。