(+/-)-1-(4-methoxyphenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one | 910028-49-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (+/-)-1-(4-methoxyphenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one
• 英文别名: (-)-1-(4-methoxyphenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one
• CAS: 910028-49-8
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: BRNHTQDDTZMPIP-SKDRFNHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.51
• 重原子数：
  15.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(4-methoxyphenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one 在 palladium on activated charcoal 三氯化铝 、 sodium azide 、 四溴化碳 、 氢气 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-(4-methoxyphenyl)cyclopropanecarboxamide
  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：

  对甲氧基苯乙醛酸 在 4-二甲氨基吡啶 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 18.25h， 生成 (+/-)-1-(4-methoxyphenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one
  参考文献：
  名称：

  烯烃束缚的 N-甲苯磺酰腙的光驱动分子内环丙烷化：稠合环丙烷 γ-内酯的合成

  摘要：

  含稠合环丙烷环的γ-内酯化合物是许多领域的通用结构单元，包括生物活性化合物的合成。在这里，我们报道了在 Cs 2 CO 3和可见光存在下，烯烃束缚的N-甲苯磺酰腙的光驱动分子内环丙烷化反应。我们采用无自由基方法，在无过渡金属的条件下以良好的收率合成了各种电子和空间取代且含杂环的稠合-(螺)环丙烷γ-内酯化合物。此外，还介绍了从α-酮酯一锅法合成稠合环丙烷γ-内酯及其合成实用性。

  DOI：

  10.1021/acs.orglett.4c02182

文献信息

• Stereocontrolled Synthesis of Trisubstituted Cyclopropanes:  Expedient, Atom-Economical, Asymmetric Syntheses of (+)-Bicifadine and DOV21947
  作者：Feng Xu、Jerry A. Murry、Bryon Simmons、Edward Corley、Kenneth Fitch、Sandor Karady、David Tschaen

  DOI：10.1021/ol061650w

  日期：2006.8.1

  An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.
• 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.
• Novel Sigma Receptor Ligands:  Synthesis and Biological Profile
  作者：Orazio Prezzavento、Agata Campisi、Simone Ronsisvalle、Giovanni Li Volti、Agostino Marrazzo、Vincenzo Bramanti、Giuseppe Cannavò、Luca Vanella、Alfredo Cagnotto、Tiziana Mennini、Riccardo Ientile、Giuseppe Ronsisvalle

  DOI：10.1021/jm0611197

  日期：2007.3.1

  The aim of the present study was to investigate the biological profile of new substituted 1-phenyl-2-cyclopropylmethylamines. High affinity for both sigma subtypes was achieved when 4-phenylpiperidin-4-ol (4a-e) and 4-benzylpiperidine moieties were present (5a-e). (1R,2S/1S,2R)-2-[4-Hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate (4b) showed high affinity for the sigma(1) sites (K-i = 1.5 nM) and the most favorable sigma(1)/sigma(2) selectivity (K-i(sigma(2))/K-i(sigma(1)) = 33.9). Binding affinity studies showed that 4b binding on N-methyl-d-aspartate (NMDA), dopaminergic (D-1, D-2, D-3), muscarinic, histaminergic H-1, adrenergic (alpha(1), alpha(2)), serotoninergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6), DA (DAT), and 5-HT (SERT) transporters was not significant. Interestingly, sigma ligands differently induced the expression of tissue transglutaminase (TG-2) in primary astroglial cell cultures. We suggest that 4b may act as a sigma(1)/sigma(2) agonist and that the sigma ligands may modulate TG-2 differently.