(+)-1-(thiophen-2-yl)-3-oxa-bicyclo[3.1.0]hexan-2-one | 942493-62-1

• 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-(thiophen-2-yl)-3-oxa-bicyclo[3.1.0]hexan-2-one
• 英文别名: (Z)-1R-(2-thienyl)-3-oxa-bicyclo[3.1.0]hexan-2-one；(1R,5R)-1-thiophen-2-yl-3-oxa-bicyclo[3.1.0]hexan-2-one；(1R,5R)-1-thiophen-2-yl-3-oxabicyclo[3.1.0]hexan-2-one
• CAS: 942493-62-1
• 化学式: C₉H₈O₂S
• 分子量: 180.227
• InChiKey: HWMYYILGECIWGS-RCOVLWMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-1-(thiophen-2-yl)-3-oxa-bicyclo[3.1.0]hexan-2-one 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
  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 盐酸 作用下， 以 水 为溶剂， 以410 g的产率得到(+)-1-(thiophen-2-yl)-3-oxa-bicyclo[3.1.0]hexan-2-one
  参考文献：
  名称：

  Characterization of Thien-2-yl 1S,2R-Milnacipran Analogues as Potent Norepinephrine/Serotonin Transporter Inhibitors for the Treatment of Neuropathic Pain

  摘要：

  Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than IS,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.

  DOI：

  10.1021/jm8009537

文献信息

• Studies on the structure–activity relationship of bicifadine analogs as monoamine transporter inhibitors
  作者：Mingzhu Zhang、Florence Jovic、Troy Vickers、Brian Dyck、Junko Tamiya、Jonathan Grey、Joe A. Tran、Beth A. Fleck、Rebecca Pick、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2008.05.077

  日期：2008.7

  Compounds with various activities and selectivities were discovered through structure -activity relationship studies of bicifadine analogs as monoamine transporter inhibitors. The norepinephrine-selective 2-thienyl compound S-6j was efficacious in a rodent pain model. (C) 2008 Elsevier Ltd. All rights reserved.
• Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors
  作者：Troy Vickers、Brian Dyck、Junko Tamiya、Mingzhu Zhang、Florence Jovic、Jonathan Grey、Beth A. Fleck、Anna Aparicio、Michael Johns、Liping Jin、Hui Tang、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2008.04.045

  日期：2008.6

  A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26 nM at NET and SERT, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• WO2007/98356
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] CONGENERS OF MILNACIPRAN AS MONOAMINE RE-UPTAKE<br/>[FR] CONGENERES DE MILNACIPRAN EN TANT QU'INHIBITEUR DE LA RECAPTURE DE MONOAMINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2007098356A1

  公开（公告）日：2007-08-30

  [EN] Monoamine re-uptake inhibitors and more specifically serotonin and noradrenaline re-uptake inhibitors are disclosed that have utility in the treatment of disorders of the central or peripheral nervous system in both men and women. The compounds of this invention have the structure: wherein R₁, R₂, R₃, R₄, R_5a, R_5b, R₆, R₇, and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts, esters and solvates thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting monoamine re-uptake in a subject in need thereof.
  [FR] L'invention concerne des inhibiteurs de la recapture de monoamine et plus précisément des inhibiteurs de la recapture de sérotonine et de noradrénaline, lesdits inhibiteurs étant utiles pour le traitement de troubles du système nerveux central ou périphérique chez les hommes et les femmes. Les composés selon cette invention présentent la structure : dans laquelle R₁, R₂, R₃, R₄, R_5a, R_5b, R₆, R₇ et n sont tels que définis dans le présent document, y compris les stéréoisomères, les promédicaments et les sels pharmaceutiquement acceptables, les esters et les solvates de ces composés. L'invention concerne également des compositions contenant un composé selon cette invention en association avec un véhicule pharmaceutiquement acceptable, ainsi que des procédés concernant l'utilisation de ces compositions pour inhiber la recapture de monoamine chez un sujet en ayant besoin.
• 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.