1-(2,4-dihydroxy-3,5-dipropylphenyl)-2,2,2-trifluoroethanone | 355387-55-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2,4-dihydroxy-3,5-dipropylphenyl)-2,2,2-trifluoroethanone
• 英文别名: 2,4-dihydroxy-3,5-dipropyl-1',1',1'-trifluoroacetophenone
• CAS: 355387-55-2
• 化学式: C₁₄H₁₇F₃O₃
• 分子量: 290.282
• InChiKey: YAKSBHSOFXBBJM-UHFFFAOYSA-N

物化性质

• 沸点：
  388.3±42.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2,4-dihydroxy-3,5-dipropylphenyl)-2,2,2-trifluoroethanone 在 吡啶 、 盐酸羟胺 、 sodium acetate 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 Methyl 2-[[5,7-dipropyl-3-(trifluoromethyl)-1,2-benzoxazol-6-yl]oxy]propanoate
  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 三氯化铝 、 氢气 、 potassium carbonate 作用下， 以 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 生成 1-(2,4-dihydroxy-3,5-dipropylphenyl)-2,2,2-trifluoroethanone
  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。
• US7495020B2
  申请人：——

  公开号：US7495020B2

  公开（公告）日：2009-02-24
• Discovery of a Novel Series of Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists for the Treatment of Type 2 Diabetes and Dyslipidemia
  作者：Kun Liu、Libo Xu、Joel P. Berger、Karen L. MacNaul、Gauchao Zhou、Thomas W. Doebber、Michael J. Forrest、David E. Moller、A. Brian Jones

  DOI：10.1021/jm048993p

  日期：2005.4.1

  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.
• O-Arylmandelic acids as highly selective human PPAR α/γ agonists
  作者：Alan D Adams、Zao Hu、Derek von Langen、Adonis Dadiz、Alex Elbrecht、Karen L MacNaul、Joel P Berger、Gaochao Zhou、Thomas W Doebber、Roger Meurer、Michael J Forrest、David E Moller、A Brian Jones

  DOI：10.1016/s0960-894x(03)00702-9

  日期：2003.10

  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.