5,7-dipropyl-6-hydroxy-3-trifluoromethyl-1,2-benzisoxazole | 355387-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 5,7-dipropyl-6-hydroxy-3-trifluoromethyl-1,2-benzisoxazole
• 英文别名: 3-(Trifluoromethyl)-5,7-dipropyl-1,2-benzoisoxazole-6-ol；5,7-dipropyl-3-(trifluoromethyl)-1,2-benzoxazol-6-ol
• CAS: 355387-57-4
• 化学式: C₁₄H₁₆F₃NO₂
• 分子量: 287.282
• InChiKey: QLOKZBKJHFKOOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  358.2±37.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,7-dipropyl-6-hydroxy-3-trifluoromethyl-1,2-benzisoxazole 在 六甲基磷酰三胺 、 caesium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 环己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.75h， 生成
  参考文献：
  名称：

  Discovery of a Novel Series of Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists for the Treatment of Type 2 Diabetes and Dyslipidemia

  摘要：

  A series of 2-aryloxy-2-methyl-propionic acid compounds and related analogues were designed, synthesized, and evaluated for their PPAR agonist activities. 2-[(5,7-Dipropyl-3-trifluoromethyl)-benzisoxazol-6-yloxy]-2-methylpropionic acid (4) was identified as a PPAR alpha/gamma dual agonist with relative PPAR alpha selectivity and demonstrated potent efficacy in lowering both glucose and lipids in animal models without causing body weight gain. The PPAR alpha activity of 4 appeared to have played a significant role in lowering glucose levels in db/db mice.

  DOI：

  10.1021/jm048993p
• 作为产物：
  描述：

  2-正丙基间苯二酚 在 palladium on activated charcoal 吡啶 、 三氯化铝 、 盐酸羟胺 、 氢气 、 sodium acetate 、 potassium carbonate 作用下， 以 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 生成 5,7-dipropyl-6-hydroxy-3-trifluoromethyl-1,2-benzisoxazole
  参考文献：
  名称：

  O-Arylmandelic acids as highly selective human PPAR α/γ agonists

  摘要：

  A new class of O-arylmandelic acid PPAR agonists show excellent anti-hyperglycemic efficacy in a db/db mouse model of DM2. These PPARalpha-weighted agonists do not show the typical PPARgamma associated side effects of BAT proliferation and cardiac hypertrophy in a rat tolerability assay. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00702-9

文献信息

• An Efficient Synthesis of a Dual PPAR α/γ Agonist and the Formation of a Sterically Congested α-Aryloxyisobutyric Acid via a Bargellini Reaction
  作者：Raymond J. Cvetovich、John Y. L. Chung、Michael H. Kress、Joseph S. Amato、Louis Matty、M. David Weingarten、Fuh-Rong Tsay、Zhen Li、George Zhou

  DOI：10.1021/jo051027+

  日期：2005.10.1

  conversion to α-aryloxyisobutyric acid 2 using 1,1,1-trichloro-2-methyl-2-propanol (chloretone) was developed. Benzisoxazole 1 was formed in high yields by the action of either methanesulfonyl chloride/base upon intermediate oxime 8 or with thionyl chloride/base, which initially forms cyclic sulfite 10. A highly reactive, short-lived intermediate derived from chloretone was detected by ReacIR and its half-life

  开发了一种实用的苯并异恶唑1的合成方法，并使用1,1,1-三氯-2-甲基-2-丙醇（氯酮）将其转化为α-芳氧基异丁酸2。通过甲烷磺酰氯/碱对中间体肟8的作用或与亚硫酰氯/碱的作用以高产率形成苯并异恶唑1，亚硫酰氯/碱最初形成环状亚硫酸盐10。通过ReacIR检测到了一种高活性，短寿命的源自丙酮的中间体，其半衰期约为5分钟。开发了Bargellini反应的反应条件，该反应条件从高度受阻的苯酚1的反应中获得95％的产率为2含丙酮半水合物和NaOH粉末状丙酮。因此，可以在一个步骤中以高收率制备高度受阻的α-芳氧基异丁酸。
• Aryloxyacetic acids for diabetes and lipid disorders
  申请人：——

  公开号：US20020173663A1

  公开（公告）日：2002-11-21

  A class of aryloxyacetic acids comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.

  一类芳基羟基乙酸类化合物包括对PPARα和/或γ具有强效激动作用的化合物，因此在治疗、控制或预防非胰岛素依赖型糖尿病（NIDDM）、高血糖、血脂异常、高血脂症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、肥胖、血管再狭窄、炎症以及其他PPARα和/或γ介导的疾病、疾病和病况中具有用处。
• 2-Aryloxy-2arylalkanoic acids for diabetes and lipid disorders
  申请人：——

  公开号：US20040092596A1

  公开（公告）日：2004-05-13

  A class of 2-aryloxy-2-arylalkanoic acids comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.

  一类2-芳氧基-2-芳基脂肪酸是PPAR alpha和/或gamma的有效激动剂，因此可用于治疗、控制或预防非胰岛素依赖性糖尿病（NIDDM）、高血糖、脂质代谢异常、高脂血症、高胆固醇血症、高三酰甘油血症、动脉粥样硬化、肥胖症、血管再狭窄、炎症和其他PPAR alpha和/或gamma介导的疾病、疾病和病况。
• 2-Aryloxy-2-arylalkanoic acids for diabetes and lipid disorders
  申请人：Adams D. Alan

  公开号：US20060122242A1

  公开（公告）日：2006-06-08

  A class of 2-aryloxy-2-arylalkanoic acids comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.

  一类2-芳氧基-2-芳基脂肪酸是一种强效PPAR alpha和/或gamma激动剂，因此可用于治疗、控制或预防非胰岛素依赖性糖尿病（NIDDM）、高血糖、失调脂质代谢、高脂血症、高胆固醇血症、高三酰甘油血症、动脉粥样硬化、肥胖症、血管再狭窄、炎症和其他PPAR alpha和/或gamma介导的疾病、疾病和状况。
• EP1259494A4
  申请人：——

  公开号：EP1259494A4

  公开（公告）日：2004-09-15