2-(4-chloro-6-(phenethylamino)pyrimidin-2-ylthio)octanoic acid | 1077626-48-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-(4-chloro-6-(phenethylamino)pyrimidin-2-ylthio)octanoic acid
• 英文别名: 2-[4-chloro-6-(2-phenylethylamino)pyrimidin-2-yl]sulfanyloctanoic acid
• CAS: 1077626-48-2
• 化学式: C₂₀H₂₆ClN₃O₂S
• 分子量: 407.964
• InChiKey: BJBAGSHQHZYGGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-((4-chloro-6-(phenethylamino)pyrimidin-2-yl)thio)octanoate 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 2-(4-chloro-6-(phenethylamino)pyrimidin-2-ylthio)octanoic acid
  参考文献：
  名称：

  Pirinixic Acid Derivatives as Novel Dual Inhibitors of Microsomal Prostaglandin E₂ Synthase-1 and 5-Lipoxygenase

  摘要：

  Dual inhibition of the prostaglandin (PG) and leukotriene (LT) biosynthetic pathway is supposed to be superior over single interference, both in terms of efficacy and side effects. Here, we present a novel class of dual microsomal PGE(2) synthase-1/5-lipoxygenase (5-LO) inhibitors based on the structure of pirinixic acid [PA, 2-(4-chloro-6-(2.3-dimethylphenylamino)pyrimidin-2-ylthio)acetic acid, compound 1]. Target-oriented structural modification of 1, particularly a substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2.3-dimethylaniline by a biphenyl-4-yl-methane-amino residue, resulted in potent suppression of mPGES-1 and 5-LO activity, exemplified by 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (7b, IC50 = 1.3 and 1 mu M, respectively). Select compounds also potently reduced PGE(2) and 5-LO product formation in intact cells. Importantly, inhibition of cyclooxygenases-1/2 was significantly less pronounced. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacologial profile and a potential for therapeutic use.

  DOI：

  10.1021/jm801085s

文献信息

• Pirinixic Acid Derivatives as Novel Dual Inhibitors of Microsomal Prostaglandin E₂ Synthase-1 and 5-Lipoxygenase
  作者：Andreas Koeberle、Heiko Zettl、Christine Greiner、Mario Wurglics、Manfred Schubert-Zsilavecz、Oliver Werz

  DOI：10.1021/jm801085s

  日期：2008.12.25

  Dual inhibition of the prostaglandin (PG) and leukotriene (LT) biosynthetic pathway is supposed to be superior over single interference, both in terms of efficacy and side effects. Here, we present a novel class of dual microsomal PGE(2) synthase-1/5-lipoxygenase (5-LO) inhibitors based on the structure of pirinixic acid [PA, 2-(4-chloro-6-(2.3-dimethylphenylamino)pyrimidin-2-ylthio)acetic acid, compound 1]. Target-oriented structural modification of 1, particularly a substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2.3-dimethylaniline by a biphenyl-4-yl-methane-amino residue, resulted in potent suppression of mPGES-1 and 5-LO activity, exemplified by 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (7b, IC50 = 1.3 and 1 mu M, respectively). Select compounds also potently reduced PGE(2) and 5-LO product formation in intact cells. Importantly, inhibition of cyclooxygenases-1/2 was significantly less pronounced. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacologial profile and a potential for therapeutic use.