3-(2-溴-5-氟苯氧基)氮杂环丁烷盐酸盐 | 1042428-83-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-(2-溴-5-氟苯氧基)氮杂环丁烷盐酸盐
• 英文名称: 3-(2-bromo-5-fluorophenoxy)azetidine hydrochloride salt
• 英文别名: 3-(2-bromo-5-fluorophenoxy)azetidine hydrochloride；3-(2-bromo-5-fluorophenoxy)azetidine;hydrochloride
• CAS: 1042428-83-0
• 化学式: C₉H₉BrFNO*ClH
• 分子量: 282.54
• InChiKey: OBOZMCYRDZSRHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.36
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-溴-5-氟苯氧基)氮杂环丁烷盐酸盐 、 6-氯哒嗪-3-甲酸甲酯 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 methyl 6-(3-(2-bromo-5-fluorophenoxy)azetidin-1-yl)pyridazine-3-carboxylate
  参考文献：
  名称：

  Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors

  摘要：

  Potent and orally bioavailable SCD inhibitors built on an azetidinyl pyridazine scaffold were identified. In a one-month gDIO mouse model of obesity, we demonstrated that there was no therapeutic index even at low doses; efficacy in preventing weight gain tracked closely with skin and eye adverse events. This was attributed to the local SCD inhibition in these tissues as a consequence of the broad tissue distribution observed in mice for this class of compounds. The search for new structural scaffolds which may display a different tissue distribution was initiated. In preparation for an HTS campaign, a radiolabeled azetidinyl pyridazine displaying low non-specific binding in the scintillation proximity assay was prepared. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.107
• 作为产物：
  描述：

  tert-butyl 3-(2-bromo-5-fluorophenoxy)azetidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 3-(2-溴-5-氟苯氧基)氮杂环丁烷盐酸盐
  参考文献：
  名称：

  [EN] AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  [FR] DÉRIVÉS D'AZÉTIDINE COMME INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE

  摘要：

  结构式I的氮杂环丙烷衍生物是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，包括心血管疾病；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；癌症；肝脂肪变性；以及非酒精性脂肪肝。

  公开号：

  WO2010043052A1

文献信息

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

  公开号：US20080182838A1

  公开（公告）日：2008-07-31

  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的氮杂环烷衍生物相对于其他已知的硬脂酰辅酶A去饱和酶(SCD1)具有选择性抑制作用。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，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；以及肝脂肪变性。
• [EN] AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] DÉRIVÉS D'AZÉTIDINE COMME INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010043052A1

  公开（公告）日：2010-04-22

  Azetidine derivatives of structural formula I are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD). 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; atherosclerosis; obesity; diabetes; neurological disease; Metabolic Syndrome; insulin resistance; cancer; liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的氮杂环丙烷衍生物是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，包括心血管疾病；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；癌症；肝脂肪变性；以及非酒精性脂肪肝。
• AZACYCLOALKANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Leblanc Yves

  公开号：US20090270434A1

  公开（公告）日：2009-10-29

  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Azacycloalkane衍生物是选择性抑制剂，针对其他已知的stearoyl-coenzyme A desaturases相对于stearoyl-coenzyme A delta-9 desaturase (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; 肥胖症; 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。
• AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Powell David

  公开号：US20110183958A1

  公开（公告）日：2011-07-28

  Azetidine derivatives of structural formula I are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD). 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; atherosclerosis; obesity; diabetes; neurological disease; Metabolic Syndrome; insulin resistance; cancer; liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的氮杂环丙烷衍生物是硬脂酰辅酶A三十九烯酸脱饱和酶（SCD）的抑制剂。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有关的疾病，包括心血管疾病；动脉粥样硬化；肥胖症；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；癌症；肝脂肪变性和非酒精性脂肪肝。
• US7582633B2
  申请人：——

  公开号：US7582633B2

  公开（公告）日：2009-09-01