Ethyl 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoate | 916482-37-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: Ethyl 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoate
• 英文别名: ethyl 2-[4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-yl]sulfanyloctanoate
• CAS: 916482-37-6
• 化学式: C₂₂H₃₀ClN₃O₂S
• 分子量: 436.018
• InChiKey: GJJDMFOJAUUPSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoate 在 乙醇 、 potassium hydroxide 作用下， 生成 2-[4-chloro-6-(2,3-dimethyl-phenylamino)-pyrimidin-2-ylsulfanyl]-octanoic acid
  参考文献：
  名称：

  Rational design of a pirinixic acid derivative that acts as subtype-selective PPARγ modulator

  摘要：

  Peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in glucose and lipid homeostasis. PPAR gamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPAR gamma modulators (SPPAR gamma Ms) was developed, which are believed to show less side effects than full PPAR gamma agonists. We have previously shown that alpha-substitution of pirinixic acid, a moderate agonist of PPAR alpha and PPAR gamma, leads to low micromolar active balanced dual agonists of PPAR alpha and PPAR alpha. Herein we present modifications of pirinixic acid leading to subtype-selective PPAR gamma agonists and furthermore the development of a selective PPAR gamma modulator guided by molecular docking studies. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.008
• 作为产物：
  描述：

  ethyl 2-[(4,6-dichloropyrimidin-2-yl)sulfanyl]octanoate 、 2,3-二甲基苯胺 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 生成 Ethyl 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)octanoate
  参考文献：
  名称：

  α-烷基取代的哌立尼克酸衍生物作为过氧化物酶体增殖物激活受体α和γ的强效双重激动剂

  摘要：

  过氧化物酶体增殖物激活受体 (PPAR) 是核受体，在能量稳态中起关键作用。PPARα 亚型激活剂广泛用于治疗高脂血症，而 PPARγ 亚型激活剂在临床上用于治疗 2 型糖尿病。由于这两种疾病经常相互关联，因此用一种同时激活 PPARα 和 PPARγ 的药物进行联合治疗似乎是值得的。从吡立昔酸开始，它是一种中等活性的双 PPARα/γ 激动剂，我们通过用脂肪链取代 α- 位来提高对人 PPARα 和 PPARγ 的效力。分别在四个碳和六个碳的链长处达到最大效果，导致 PPARα 的活性诱导因子分别为 36 和 PPARγ 的因子为 18。

  DOI：

  10.1002/ardp.200700209

文献信息

• α-Alkyl Substituted Pirinixic Acid Derivatives as Potent Dual Agonists of the Peroxisome Proliferator Activated Receptor Alpha and Gamma
  作者：Oliver Rau、Yvonne Syha、Heiko Zettl、Michael Kock、Andreas Bock、Manfred Schubert-Zsilavecz

  DOI：10.1002/ardp.200700209

  日期：2008.3

  Peroxisome proliferator‐activated receptors (PPAR) are nuclear receptors, playing a pivotal role in energy homeostasis. Activators of the PPARα subtype are in widespread use for the treatment of hyperlipidemia, while activators of the PPARγ subtype are in clinical use for the treatment of type‐2 diabetes. Since both of these diseases are frequently associated, the combined treatment with one drug simultaneously

  过氧化物酶体增殖物激活受体 (PPAR) 是核受体，在能量稳态中起关键作用。PPARα 亚型激活剂广泛用于治疗高脂血症，而 PPARγ 亚型激活剂在临床上用于治疗 2 型糖尿病。由于这两种疾病经常相互关联，因此用一种同时激活 PPARα 和 PPARγ 的药物进行联合治疗似乎是值得的。从吡立昔酸开始，它是一种中等活性的双 PPARα/γ 激动剂，我们通过用脂肪链取代 α- 位来提高对人 PPARα 和 PPARγ 的效力。分别在四个碳和六个碳的链长处达到最大效果，导致 PPARα 的活性诱导因子分别为 36 和 PPARγ 的因子为 18。
• Rational design of a pirinixic acid derivative that acts as subtype-selective PPARγ modulator
  作者：Theresa M. Thieme、Ramona Steri、Ewgenij Proschak、Alexander Paulke、Gisbert Schneider、Manfred Schubert-Zsilavecz

  DOI：10.1016/j.bmcl.2010.03.008

  日期：2010.4

  Peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in glucose and lipid homeostasis. PPAR gamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPAR gamma modulators (SPPAR gamma Ms) was developed, which are believed to show less side effects than full PPAR gamma agonists. We have previously shown that alpha-substitution of pirinixic acid, a moderate agonist of PPAR alpha and PPAR gamma, leads to low micromolar active balanced dual agonists of PPAR alpha and PPAR alpha. Herein we present modifications of pirinixic acid leading to subtype-selective PPAR gamma agonists and furthermore the development of a selective PPAR gamma modulator guided by molecular docking studies. (C) 2010 Elsevier Ltd. All rights reserved.