3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxylic acid amide | 1030613-34-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxylic acid amide
• 英文别名: 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxamide；3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydro-1,2-oxazole-5-carboxamide
• CAS: 1030613-34-3
• 化学式: C₁₅H₁₇BrFN₃O₃
• 分子量: 386.221
• InChiKey: ZCDIFCCEMBOGBC-UHFFFAOYSA-N

物化性质

• 沸点：
  524.2±60.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxylic acid amide 在 甲酸 、 sodium azide 、 三乙胺 、 zinc(II) oxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 水 为溶剂， 反应 10.58h， 生成 2H-四唑乙酸,5-[3-[4-(2-溴-5-氟苯氧基)-1-哌啶基]-5-异恶唑]-
  参考文献：
  名称：

  Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245

  摘要：

  A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.

  DOI：

  10.1021/op200186d
• 作为产物：
  描述：

  1-溴-2,4-二氟苯 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 24.34h， 生成 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxylic acid amide
  参考文献：
  名称：

  Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245

  摘要：

  A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.

  DOI：

  10.1021/op200186d

文献信息

• Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
  申请人：Lachance Nicolas

  公开号：US20080132542A1

  公开（公告）日：2008-06-05

  Azacycloalkane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式I的氮代环烷衍生物是选择性抑制剂，相对于其他已知的硬脂酰辅酶A delta-9去饱和酶（SCD1）。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病，如动脉粥样硬化；肥胖；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；和肝脂肪变性。
• Org. Process Res. Dev. 2011, 15, 1073-1080
  作者：

  DOI：——

  日期：——
• AZACYCLOALKANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Merck Canada Inc.

  公开号：EP2099793B1

  公开（公告）日：2012-02-01
• US8063224B2
  申请人：——

  公开号：US8063224B2

  公开（公告）日：2011-11-22
• [EN] AZACYCLOALKANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] DÉRIVÉS D'AZACYCLOALKANE UTILISÉS COMME INHIBITEURS DE LA COENZYME A DELTA-9 DÉSATURASE-STEAROYLE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2008064474A1

  公开（公告）日：2008-06-05

  [EN] Azacycloalkane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.
  [FR] L'invention porte sur des dérivés d'azacycloalkane de la formule structurelle I qui sont des inhibiteurs sélectifs de la coenzyme A delta-9 désaturase- stearoyle (SCD1) par rapport aux autres coenzymes A désaturases-stearoyles connues. Les composés de l'invention sont utilisés pour prévenir et traiter les états liés à une synthèse et un métabolisme anormaux des lipides, y compris la maladie cardiovasculaire, par exemple l'athérosclérose, l'obésité, le diabète, la maladie neurologique, le syndrome métabolique, la résistance à l'insuline et la stéatose hépatique.