贝氟沙通 | 134564-82-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 贝氟沙通
• 英文名称: befloxatone
• 英文别名: ((R)-5-(methoxymethyl)-3(4-((R)-4,4,4-trifluoro-3-hydroxybutoxy)phenyl)-oxazolidin-2-one)；(R)-5-(methoxymethyl)-3-(4-((R)-4,4,4-trifluoro-3-hydroxybutoxy)phenyl)-oxazolidin-2-one；(R)-5-(methoxymethyl)-3-(p[(R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl)-2-oxazolidinone；(5R)-5-(methoxymethyl)-3-[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]-1,3-oxazolidin-2-one
• CAS: 134564-82-2
• 化学式: C₁₅H₁₈F₃NO₅
• 分子量: 349.307
• InChiKey: IALVDLPLCLFBCF-CHWSQXEVSA-N

物化性质

• 熔点：
  101°
• 比旋光度：
  D20 -11.5° (c = 1 in methylene chloride)
• 沸点：
  447.3±45.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  8

制备方法与用途

贝氟沙酮（MD-370503）是一种口服活性、选择性和可逆的单胺氧化酶A（MAO-A）抑制剂（IC50=4nM）。该化合物能够增加组织中单胺类物质的水平，并特别提高纹状体多巴胺和皮质去甲肾上腺素的含量。研究表明，贝氟沙酮具有抗抑郁作用。

反应信息

• 作为反应物：
  描述：

  贝氟沙通 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以78%的产率得到(R)-1-methoxy-3-[[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]amino]-2-propanol
  参考文献：
  名称：

  Synthesis and in vivo imaging properties of [11C]befloxatone: A novel highly potent positron emission tomography ligand for mono-amine oxidase-A

  摘要：

  Befloxatone (1, (5R)-5-(methoxymethyl)-3-[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]-2-oxazolidinone) is an oxazolidinone derivative belonging to a new generation of reversible and selective mono-amine oxidase-A (MAO-A) inhibitors. In vitro and ex vivo studies have demonstrated that befloxatone is a potent, reversible and competitive MAO-A inhibitor with potential antidepressant properties. Befloxatone (1) was labelled with carbon-11 (t(1/2): 20.4min) using [C-11]phosgene as reagent. Typically, starting from a 1.2Ci (44.4GBq) cyclotron-produced [C-11]CH4 batch, 150-3OOmCi (5.55-11.10 GBq) of [C-11]befloxatone ([C-11]-1) with a radiochemical- and chemical purity of more than 99% were routinely obtained within 20min of radiosynthesis (including HPLC purification) with specific radioactivities of 500-20OOmCi/mumol (18.5-74.0GBq/mumol). The results obtained in vivo with carbon-11-labelled befloxatone not only confirm the biochemical and pharmacological profile of befloxatone found in rodent and in human tissues but also point out [C-11]befloxatone as an excellent tool for the assessment of MAO-A binding sites using positron emission tomography, a high-resolution, sensitive, non-invasive and quantitative imaging technique. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00215-4
• 作为产物：
  描述：

  (R)-3-(4-(benzyloxy)phenyl)-5-(methoxymethyl)oxazolidin-2-one 在 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 贝氟沙通
  参考文献：
  名称：

  Practical synthesis of 4,4,4-trifluorocrotonaldehyde: a versatile precursor for the enantioselective formation of trifluoromethylated stereogenic centers via organocatalytic 1,4-additions

  摘要：

  报道了4,4,4-三氟巴豆醛（1）的实际合成及其在不对称1,4-加成反应中的应用。通过有机催化剂催化的1,4-加成反应，1与多种亲核试剂如杂芳香化合物、烷硫醇和醛肟反应，生成了各自带有高光学纯度的三氟甲基化手性中心的相应产物。其中一个产物被转化为MAO-A抑制剂贝氟沙酮。

  DOI：

  10.1039/c2cc32757k

文献信息

• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions
  申请人：Graziano P. Michael

  公开号：US20050096307A1

  公开（公告）日：2005-05-05

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one lipid modulating agent; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种脂质调节剂；和(b)至少一种取代的噁唑烷酮或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖以及降低血浆中甾醇或5α-甾烷醇的水平。
• Combinations of substituted azetidinones and CB1 antagonists
  申请人：Veltri P. Enrico

  公开号：US20060069080A1

  公开（公告）日：2006-03-30

  The present invention provides compositions, therapeutic combinations and methods including: (a) at least one selective CB 1 antagonist; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity, metabolic syndrome and lowering plasma levels of sterols or 5α-stanols.

  本发明提供了包括以下内容的组合物、治疗组合和方法：(a)至少一种选择性CB1拮抗剂；和(b)至少一种取代的氮杂环丁烷或取代的β-内酰胺甾醇吸收抑制剂，可用于治疗血管疾病、糖尿病、肥胖、代谢综合征以及降低血浆中的甾醇或5α-甾烷醇水平。
• Heteroaryl-Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
  申请人：Pfizer Inc.

  公开号：US20140228356A1

  公开（公告）日：2014-08-14

  The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, and the variables R 1 and R 2 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本发明涉及所披露的化合物、互变异构体和该化合物的药用可接受盐，其中该化合物具有如下式的结构， 变量R1和R2如规范中所定义。还披露了相应的药用组合物、治疗方法、合成方法和中间体。
• Heterocyclic Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
  申请人：PFIZER INC.

  公开号：US20130296308A1

  公开（公告）日：2013-11-07

  Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  揭示了化合物、互变异构体和该化合物的药学上可接受的盐，其中该化合物具有如规范中定义的Formula I的结构。还披露了相应的药物组合物、治疗方法、合成方法和中间体。