3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile | 1030613-38-7

• 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]isoxazole-5-carbonitrile
• 英文别名: 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,2-oxazole-5-carbonitrile
• CAS: 1030613-38-7
• 化学式: C₁₅H₁₃BrFN₃O₂
• 分子量: 366.19
• InChiKey: LMLAASFWFVMDLM-UHFFFAOYSA-N

物化性质

• 沸点：
  497.2±45.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  62.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile 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 4.83h， 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：

  3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxylic acid amide 在 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile
  参考文献：
  名称：

  Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase

  摘要：

  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。

  公开号：

  US20080132542A1

文献信息

• Development of a Liver-Targeted Stearoyl-CoA Desaturase (SCD) Inhibitor (MK-8245) to Establish a Therapeutic Window for the Treatment of Diabetes and Dyslipidemia
  作者：Renata M. Oballa、Liette Belair、W. Cameron Black、Kelly Bleasby、Chi Chung Chan、Carole Desroches、Xiaobing Du、Robert Gordon、Jocelyne Guay、Sebastien Guiral、Michael J. Hafey、Emelie Hamelin、Zheng Huang、Brian Kennedy、Nicolas Lachance、France Landry、Chun Sing Li、Joseph Mancini、Denis Normandin、Alessandro Pocai、David A. Powell、Yeeman K. Ramtohul、Kathryn Skorey、Dan Sørensen、Wayne Sturkenboom、Angela Styhler、Deena M. Waddleton、Hao Wang、Simon Wong、Lijing Xu、Lei Zhang

  DOI：10.1021/jm200319u

  日期：2011.7.28

  The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.
• Org. Process Res. Dev. 2011, 15, 1073-1080
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 2011, 54, 5082-5096
  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