1-(4-Hydroxy-3,5-dipropylphenyl)-2,2-dimethyl-1-propanone | 1026056-19-8

• 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)-2,2-dimethyl-1-propanone
• 英文别名: 1-(4-hydroxy-3,5-dipropylphenyl)-2,2-dimethylpropan-1-one
• CAS: 1026056-19-8
• 化学式: C₁₇H₂₆O₂
• 分子量: 262.392
• InChiKey: GNOFPBUJYUGOQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 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)-2,2-dimethyl-1-propanone 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 [4-(2,2-Dimethyl-propionyl)-2,6-dipropyl-phenoxy]-phenyl-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 、 特戊酸钠 在 三氟甲磺酸 作用下， 反应 1.0h， 生成 1-(4-Hydroxy-3,5-dipropylphenyl)-2,2-dimethyl-1-propanone
  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

文献信息

• Design and Synthesis of α-Aryloxyphenylacetic Acid Derivatives:  A Novel Class of PPARα/γ Dual Agonists with Potent Antihyperglycemic and Lipid Modulating Activity
  作者：Guo Q. Shi、James F. Dropinski、Brian M. McKeever、Shihua Xu、Joseph W. Becker、Joel P. Berger、Karen L. MacNaul、Alex Elbrecht、Gaochao Zhou、Thomas W. Doebber、Peiran Wang、Yu-Sheng Chao、Mike Forrest、James V. Heck、David E. Moller、A. Brian Jones

  DOI：10.1021/jm0502135

  日期：2005.6.1

  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.