ethyl 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoate | 1077626-58-4

• 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: ethyl 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoate
• 英文别名: Ethyl 2-[4-chloro-6-[4-(4-cyanophenyl)anilino]pyrimidin-2-yl]sulfanyloctanoate
• CAS: 1077626-58-4
• 化学式: C₂₇H₂₉ClN₄O₂S
• 分子量: 509.072
• InChiKey: RQBQMDHKHOOATA-UHFFFAOYSA-N

物化性质

• 沸点：
  647.1±55.0 °C(predicted)
• 密度：
  1.26±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoate 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)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
• 作为产物：
  描述：

  ethyl 2-[(4,6-dichloropyrimidin-2-yl)sulfanyl]octanoate 、 4'-氨基-4-氰基联苯 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 96.0h， 以60%的产率得到ethyl 2-(4-chloro-6-(4'-cyanobiphenyl-4-ylamino)pyrimidin-2-ylthio)octanoate
  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.