(+/-)-1-(4-chlorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one

• 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: (+/-)-1-(4-chlorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one
• 英文别名: (1R,5S)-1-(4-chlorophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
• 化学式: C₁₁H₉ClO₂
• 分子量: 208.644
• InChiKey: HEMWVVNJMILOET-KCJUWKMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(4-chlorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one 在 重铬酸吡啶 、 硼烷四氢呋喃络合物 、 4 A molecular sieve 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 15.33h， 生成 (1R,5S)-3-(tert-butoxycarbonyl)-1-(4-chlorophenyl)-3-azabicyclo[3.1.0]hexan-2-one
  参考文献：
  名称：

  Synthesis of Conformationally Restricted Analogs of Baclofen, a Potent GABAB Receptor Agonist, by the Introduction of a Cyclopropane Ring.

  摘要：

  设计了一些构象受限的baclofen (2) 类似物，即5、6及其对映体ent-5和ent-6，通过引入环丙烷环来限制其构象，作为潜在的GABAB受体配体。在苯/四氢呋喃的存在下，(R)-环氯醇[(R)-7]与(4-氯苯基)乙腈在NaNH₂的作用下反应，得到手性环丙烷衍生物11和12，随后分别将其转化为目标化合物5和6。它们对应的对映体ent-5和ent-6也以(S)-环氯醇[(S)-7]为起始物合成。

  DOI：

  10.1248/cpb.47.1188
• 作为产物：
  描述：

  allyl 2-(4-chlorophenyl)-2-diazoacetate 在 辛酸铑 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (+/-)-1-(4-chlorophenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one
  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

• 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.
• 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.
• 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.
• Synthesis of Conformationally Restricted Analogs of Baclofen, a Potent GABAB Receptor Agonist, by the Introduction of a Cyclopropane Ring.
  作者：Satoshi SHUTO、Nobuko SHIBUYA、Shizuo YAMADA、Takashi OHKURA、Ryohei KIMURA、Akira MATSUDA

  DOI：10.1248/cpb.47.1188

  日期：——

  Conformationally restricted analogs of baclofen (2), i.e., 5, 6, and their enantiomers ent-5, and ent-6, the conformations of which were restricted by introducing a cyclopropane ring, were designed as potential GABAB receptor ligands. Reaction of (R)-epichlorohydrin [(R)-7] and (4-chlorophenyl)acetonitrile in the presence of NaNH-2, in benzene/tetrahydrofuran gave chiral cyclopropane derivatives 11 and 12, which were then converted into the target compounds 5 and 6, respectively. Their corresponding enantiomers, ent-5 and ent-6, were also synthesized starting from (S)-epichlorohydring [(S)-7].

  设计了一些构象受限的baclofen (2) 类似物，即5、6及其对映体ent-5和ent-6，通过引入环丙烷环来限制其构象，作为潜在的GABAB受体配体。在苯/四氢呋喃的存在下，(R)-环氯醇[(R)-7]与(4-氯苯基)乙腈在NaNH₂的作用下反应，得到手性环丙烷衍生物11和12，随后分别将其转化为目标化合物5和6。它们对应的对映体ent-5和ent-6也以(S)-环氯醇[(S)-7]为起始物合成。
• 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.