| 1060280-11-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1060280-11-6
• 化学式: C₁₅H₁₉NO₄S
• 分子量: 309.386
• InChiKey: KTWNLMYOQBZFIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  69.4
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  、 丙二酸二乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Modulation of PPAR receptor subtype selectivity of the ligands: Aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety

  摘要：

  Oxazole containing glycine and oximinobutyric acid derivatives were synthesized as PPAR alpha agonists by incorporating polymethylene spacer as a replacement of commonly used phenylene group that connects the acidic head with lipophilic tail. Compound 13a was found to be a selective and potent PPAR alpha agonist. Further 1,3-dioxane-2-carboxylic acid derivative 20 was synthesized by replacing the tetramethylene spacer of NS-220, a selective PPAR alpha agonist with phenylene group and found to exhibit PPAR alpha/gamma dual agonism. These results suggest that compounds possessing polymethylene spacer between pharmacophore and lipophilic tail exhibit predominantly PPARa agonism whereas those with an aromatic phenylene spacer shows PPAR alpha/gamma dual agonism. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.062
• 作为产物：
  描述：

  3-[5-Methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]propan-1-ol 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Modulation of PPAR receptor subtype selectivity of the ligands: Aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety

  摘要：

  Oxazole containing glycine and oximinobutyric acid derivatives were synthesized as PPAR alpha agonists by incorporating polymethylene spacer as a replacement of commonly used phenylene group that connects the acidic head with lipophilic tail. Compound 13a was found to be a selective and potent PPAR alpha agonist. Further 1,3-dioxane-2-carboxylic acid derivative 20 was synthesized by replacing the tetramethylene spacer of NS-220, a selective PPAR alpha agonist with phenylene group and found to exhibit PPAR alpha/gamma dual agonism. These results suggest that compounds possessing polymethylene spacer between pharmacophore and lipophilic tail exhibit predominantly PPARa agonism whereas those with an aromatic phenylene spacer shows PPAR alpha/gamma dual agonism. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.062

文献信息

• Design and synthesis of novel oxazole containing 1,3-Dioxane-2-carboxylic acid derivatives as PPAR α/γ dual agonists
  作者：Harikishore Pingali、Mukul Jain、Shailesh Shah、Pankaj Makadia、Pandurang Zaware、Ashish Goel、Megha Patel、Suresh Giri、Harilal Patel、Pankaj Patel

  DOI：10.1016/j.bmc.2008.06.050

  日期：2008.8

  A few novel 1,3-dioxane carboxylic acid derivatives were designed and synthesized to aid in the characterization of PPAR alpha/gamma dual agonists. Structural requirements for PPARalpha/gamma dual agonism of 1,3-dioxane carboxylic acid derivatives included the structural similarity with potent glitazones in fibric acid chemotype. The compounds with this pharmacophore and substituted oxazole as a lipophilic

  设计和合成了一些新颖的1,3-二恶烷羧酸衍生物，以帮助表征PPARα/γ双激动剂。1,3-二恶烷羧酸衍生物的PPARalpha /γ双激动性的结构要求包括与强酸格列酮在纤维酸化学型中的结构相似性。合成了具有该药效团和取代的恶唑作为亲脂性杂环尾巴的化合物，并在动物模型中评估了其体外PPAR激动剂的潜力以及体内降血糖和降血脂的功效。铅化合物2-甲基-c-5- [4-（5-（甲基-2-（4-甲基苯基）-恶唑-4-基甲氧基）-苄基] -1,3-二恶烷-r-2-羧酸13b在db / db小鼠和Zucker fa / fa大鼠中表现出有效的降血糖，降血脂和胰岛素增敏作用。