1-(4-hydroxy-3,5-dipropylphenyl)propan-1-one | 449779-75-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-hydroxy-3,5-dipropylphenyl)propan-1-one
• 英文别名: 2,6-Dipropyl4-propionylphenol
• CAS: 449779-75-3
• 化学式: C₁₅H₂₂O₂
• 分子量: 234.338
• InChiKey: HLCUBQBQGVLRKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxy-3,5-dipropylphenyl)propan-1-one 在 lithium hydroxide 、 双氧水 、 lithium tert-butoxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (S)-(4-Isopropyl-phenyl)-(4-propionyl-2,6-dipropyl-phenoxy)-acetic acid
  参考文献：
  名称：

  Design and Synthesis of α-Aryloxyphenylacetic Acid Derivatives:  A Novel Class of PPARα/γ Dual Agonists with Potent Antihyperglycemic and Lipid Modulating Activity

  摘要：

  The synthesis and structure-activity relationships of novel series of alpha-aryloxyphenylacetic acids as PPARalpha/gamma dual agonists are reported. The initial search for surrogates of the ester group in the screen lead led first to the optimization of a subseries with a ketone moiety. Further efforts to modify the ketone subseries led to the design and synthesis of two new subseries containing fused heterocyclic ring systems. All these analogues were characterized by their "super" PPARalpha agonist activity and weak or partial agonist activity on PPARgamma in PPAR-GAL4 transactivation assays despite their similar binding affinities for both receptors. The cocrystal structures of compounds 7 and rosiglitazone with PPARgamma-LBD were compared, and significant differences were found in their interactions with the receptor. Select analogues in each subseries were further evaluated for in vivo efficacy. They all showed excellent anti-hyperglycemic efficacy in a db/db mouse model and hypolipidemic activity in hamster and dog models without provoking the typical PPARgamma-associated side effects in the rat tolerability assay.

  DOI：

  10.1021/jm0502135
• 作为产物：
  描述：

  2,6-二丙基苯酚 、 sodium proprionate 在 silica gel 作用下， 以 三氟甲磺酸 为溶剂， 生成 1-(4-hydroxy-3,5-dipropylphenyl)propan-1-one
  参考文献：
  名称：

  2-aryloxy-2-arylalkanoic acids for diabetes and lipid disorders

  摘要：

  一类2-芳氧基-2-芳基烷酸是一种有效的PPARα和/或γ受体激动剂，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、血脂异常、高脂血症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、肥胖症、血管再狭窄、炎症和其他PPARα和/或γ介导的疾病、疾病和状况。

  公开号：

  US07091230B2

文献信息

• 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。
• 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.
• EP1366012A4
  申请人：——

  公开号：EP1366012A4

  公开（公告）日：2005-11-02
• 2-ARYLOXY-2-ARYLALKANOIC ACIDS FOR DIABETES AND LIPID DISORDERS
  申请人：Merck & Co., Inc.

  公开号：EP1366012A2

  公开（公告）日：2003-12-03