(1R,5S)-2-oxo-1-(4-fluorophenyl)-3-oxabicyclo[3.1.0]hexane | 942493-37-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (1R,5S)-2-oxo-1-(4-fluorophenyl)-3-oxabicyclo[3.1.0]hexane
• 英文别名: (-)-1-(4-fluorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one；(1R,5S)-1-(4-Fluorophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
• CAS: 942493-37-0
• 化学式: C₁₁H₉FO₂
• 分子量: 192.19
• InChiKey: MEGHXTJNUVAMGQ-KCJUWKMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,5S)-2-oxo-1-(4-fluorophenyl)-3-oxabicyclo[3.1.0]hexane 在 三氯化铝 、 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (1R,2S)-2-(bromomethyl)-N,N-diethyl-1-(4-fluorophenyl)cyclopropane-1-carboxamide
  参考文献：
  名称：

  Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

  摘要：

  A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantionteric excess. Structure-activity relationships for two parallel enantionteric series are described. The (-)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.054
• 作为产物：
  描述：

  在 辛酸铑 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (1R,5S)-2-oxo-1-(4-fluorophenyl)-3-oxabicyclo[3.1.0]hexane
  参考文献：
  名称：

  Identification of a new series of non-peptidic NK3 receptor antagonists

  摘要：

  The identification and structure-activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK3 receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK3 receptor and brain exposure, leading to activity in vivo in the senktide-induced hypoactivity model in gerbils. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.135

文献信息

• Synthesis of derivatives of (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) modified at the 1-aromatic moiety as novel NMDA receptor antagonists: the aromatic group is essential for the activity
  作者：Yuji Kazuta、Ryuichi Tsujita、Kanako Yamashita、Shigeo Uchino、Shinichi Kohsaka、Akira Matsuda、Satoshi Shuto

  DOI：10.1016/s0968-0896(02)00346-2

  日期：2002.12

  (1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC. 4a). which is a conformationally restricted analogue of antidepressant milnacipran [(+/-)-1]. is a new class of potent noncompetitive NMDA receptor antagonists. A series of PPDC analogues modified at the 1-phenyl moiety. that is, the analogue 6 lacking 1-phenyl group, the 1-(fluorophenyl) analogues 4b,c.d. the 1-(methylphenyl) analogues 4e-g and the 1-(naphthyl) analogues 4h.i were synthesized. Analogue 6. lacking the 1-phenyl group. was completely inactive showing that the aromatic moiety is essential for the NMDA receptor binding. Among the analogues synthesized, the 1-o-fluorophenyl and 1-m-fluorophenyl analogues 4b and 4c showed potent affinities for the NMDA receptor [IC50=0.16+/-0.001 muM (4b), 0.15+/-0.02 muM (4c)]. which were improved to some extent compared to those of the parent compound PPDC (IC50=0.20+/-0.02 muM). On the other hand, compounds 4b and 4c showed none of the 5-HT-uptake inhibitors effect, while PPDC turned out to be a weak 5-HT-uptake inhibitor. (C) 2002 Elsevier Science Ltd. All rights reserved.

  (1S,2R)-1-苯基-2-[(S)-1-氨基丙基]-N,N-二乙基环丙烷甲酰胺（PPDC. 4a），作为一种结构受限的抗抑郁药米那西普兰[（+/-）-1]类似物，是一种新型的强效非竞争性NMDA受体拮抗剂。在1-苯基部分进行了修饰的PPDC类似物系列被合成，即缺乏1-苯基基团的类似物6，1-(氟代苯基)类似物4b、c、d，1-(甲基苯基)类似物4e-g，以及1-(萘基)类似物4h、i。类似物6，缺乏1-苯基基团，完全表现出无活性，表明芳香基团对于NMDA受体的结合是必需的。在合成的类似物中，1-o-氟代苯基和1-m-氟代苯基类似物4b和4c显示了对NMDA受体的显著亲和力[IC50=0.16+/-0.001 μM（4b），0.15+/-0.02 μM（4c）]，相较于母体化合物PPDC（IC50=0.20+/-0.02 μM）有所提高。另一方面，化合物4b和4c未显示出5-HT摄取抑制效应，而PPDC则表现出较弱的5-HT摄取抑制作用。（C）2002 Elsevier Science Ltd. 保留所有权利。
• Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters
  作者：Heidi Roggen、Jan Kehler、Tine Bryan Stensbøl、Tore Hansen

  DOI：10.1016/j.bmcl.2007.02.054

  日期：2007.5

  A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantionteric excess. Structure-activity relationships for two parallel enantionteric series are described. The (-)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT. (c) 2007 Elsevier Ltd. All rights reserved.
• Identification of a new series of non-peptidic NK3 receptor antagonists
  作者：Karsten Juhl、Tore Hansen、Jan Kehler、Nikolay A. Khanzhin、Morten B. Nørgaard、Thomas Ruhland、Dorrit B. Larsen、Klaus G. Jensen、Björn Steiniger-Brach、Søren M. Nielsen、Klaus B. Simonsen

  DOI：10.1016/j.bmcl.2010.12.135

  日期：2011.3

  The identification and structure-activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK3 receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK3 receptor and brain exposure, leading to activity in vivo in the senktide-induced hypoactivity model in gerbils. (C) 2011 Elsevier Ltd. All rights reserved.