2,4-di-n-propylbenzene-1,3-diol | 355387-54-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4-di-n-propylbenzene-1,3-diol
• 英文别名: 2,4-bis(n-propyl)resorcinol；2,4-di-n-propylresorcinol；2,4-dipropylresorcinol；2,6-dipropylresorcinol；2,4-dipropylbenzene-1,3-diol
• CAS: 355387-54-1
• 化学式: C₁₂H₁₈O₂
• 分子量: 194.274
• InChiKey: JJWMIFAPVZNHOT-UHFFFAOYSA-N

物化性质

• 沸点：
  339.1±12.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-di-n-propylbenzene-1,3-diol 在 palladium on activated charcoal 吡啶 、 lithium hydroxide 、 氢气 、 双氧水 、 溶剂黄146 、 乙酰氯 、 lithium tert-butoxide 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -30.0~25.0 ℃ 、101.33 kPa 条件下， 反应 25.5h， 生成 (S)-(4-Chloro-phenyl)-(3-ethyl-2-oxo-5,7-dipropyl-2,3-dihydro-benzooxazol-6-yloxy)-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：

  5-壬酮 生成 2,4-di-n-propylbenzene-1,3-diol
  参考文献：
  名称：

  Aryloxyacetic acids for diabetes and lipid disorders

  摘要：

  一类芳氧基乙酸包括一些化合物，它们是PPARα和/或γ的有效激动剂，因此在治疗、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、疾患和情况中有用。

  公开号：

  US06569879B2

文献信息

• Design and discovery of 2-oxochromene derivatives as liver X receptor β-selective agonists
  作者：Takayuki Matsuda、Ayumu Okuda、Yuichiro Watanabe、Tohru Miura、Hidefumi Ozawa、Ayako Tosaka、Koichi Yamazaki、Yuki Yamaguchi、Sayaka Kurobuchi、Minoru Koura、Kimiyuki Shibuya

  DOI：10.1016/j.bmcl.2015.01.047

  日期：2015.3

  an attempt to molecularly design liver X receptor (LXR) β-selective agonists, we discovered that the combination of the 2-oxochromene moiety (head) and the imidazoline-2,4-dione moiety (tail) plays an important role in the expression potency and selectivity toward LXRβ. We synthesized a series of 2-oxochromene derivatives and identified 43 as a LXRβ-selective agonist that increased the HDL-C level without

  在分子设计肝X受体（LXR）β-选择性激动剂的尝试中，我们发现2-氧代色烯部分（头部）和咪唑啉-2,4-二酮部分（尾巴）的组合在表达能力和对LXRβ的选择性。我们合成了一系列2-oxochromene衍生物，并确定了43种LXRβ选择性激动剂，可在不显着升高TG水平的情况下增加HDL-C水平，并导致高脂饮食中主动脉弓内脂质蓄积面积减少。和胆固醇喂养的Bio F 1 B仓鼠。在这份手稿中，我们报告了这些2-氧代苯并二氢吡喃衍生物的设计，合成和药理作用。
• Effect of <i>ortho</i>-SR Groups on O−H Bond Strength and H-Atom Donating Ability of Phenols:  A Possible Role for the Tyr-Cys Link in Galactose Oxidase Active Site?
  作者：Riccardo Amorati、Francesca Catarzi、Stefano Menichetti、Gian Franco Pedulli、Caterina Viglianisi

  DOI：10.1021/ja075554h

  日期：2008.1.1

  dissociation enthalpy (BDE) and the reactivity of the OH group. Newly synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost coplanar with the phenolic ring, are characterized by unusually low BDE(O-H) values (79.6 and 79.2 kcal/mol, respectively) and by much higher reactivities toward peroxyl radicals than the ortho-methylthio derivative 1 (82.0 kcal/mol). The importance of

  邻（烷硫基）苯酚中 Ar-S 键的旋转强烈影响键解离焓 (BDE) 和 OH 基团的反应性。新合成的含硫杂环 3 和 4，其中 -SR 基团几乎与酚环共面，其特征在于异常低的 BDE(OH) 值（分别为 79.6 和 79.2 kcal/mol）和对过氧自由基的高得多的反应性比邻甲硫基衍生物 1 (82.0 kcal/mol)。FT-IR 实验证明了分子内氢键 (IHB) 在确定 BDE(OH) 中的重要性，这表明在杂环 3 和 4 中，酚 OH 基团和 S 原子之间的 IHB 比目前的要弱得多在 1. 由于只有 -SR 组采用平面外几何结构才能形成 IHB，这种相互作用仅在甲硫基衍生物 1 中是可能的，而不是在 3 和 4 中。 因此，-SR 取代基对酚类 BDE(OH) 的附加贡献从 -3.1 到 +2.8 kcal/mol 变化为面内和平面构象，分别。这些结果可能与理解半乳糖氧化酶活
• 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。
• 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。