ethyl 2-(4-chloro-6-(2,3-dihydro-1H-inden-5-ylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetate | 1228298-41-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: ethyl 2-(4-chloro-6-(2,3-dihydro-1H-inden-5-ylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetate
• CAS: 1228298-41-6
• 化学式: C₂₇H₂₄ClN₃O₂S
• 分子量: 490.025
• InChiKey: KEFLDJFPJAEKKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.91
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  64.11
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-chloro-6-(2,3-dihydro-1H-inden-5-ylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetate 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-(4-chloro-6-(2,3-dihydro-1H-inden-5-ylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetic acid
  参考文献：
  名称：

  A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold

  摘要：

  Dual inhibition of microsomal prostaglandin E-2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) represents a promising strategy in the development of novel anti-inflammatory drugs targeting the arachidonic acid cascade. Herein, a class of alpha-naphthyl pirinixic acids is characterized as dual mPGES-1/5-LO inhibitors. Systematic structural variation was focused on the lipophilic backbone of the scaffold and yielded detailed structure-activity relationships (SAR) with compound 16 (IC50 mPGES-1 = 0.94 mu M; IC50 5-LO = 0.1 mu M) showing the most favorable in vitro pharmacological profile. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.049
• 作为产物：
  描述：

  Alpha-溴代-1-萘乙酸乙酯 在 三乙胺 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 ethyl 2-(4-chloro-6-(2,3-dihydro-1H-inden-5-ylamino)pyrimidin-2-ylthio)-2-(naphthalen-1-yl)acetate
  参考文献：
  名称：

  A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold

  摘要：

  Dual inhibition of microsomal prostaglandin E-2 synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) represents a promising strategy in the development of novel anti-inflammatory drugs targeting the arachidonic acid cascade. Herein, a class of alpha-naphthyl pirinixic acids is characterized as dual mPGES-1/5-LO inhibitors. Systematic structural variation was focused on the lipophilic backbone of the scaffold and yielded detailed structure-activity relationships (SAR) with compound 16 (IC50 mPGES-1 = 0.94 mu M; IC50 5-LO = 0.1 mu M) showing the most favorable in vitro pharmacological profile. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.049

文献信息

• 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.