Methyl 4-(2-methylphenyl)-5-oxo-5-[3-(pyridin-4-ylmethoxy)phenyl]pentanoate | 170280-05-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: Methyl 4-(2-methylphenyl)-5-oxo-5-[3-(pyridin-4-ylmethoxy)phenyl]pentanoate
• CAS: 170280-05-4
• 化学式: C₂₅H₂₅NO₄
• 分子量: 403.478
• InChiKey: KCCUUYIVJUNZGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl 4-(2-methylphenyl)-5-oxo-5-[3-(pyridin-4-ylmethoxy)phenyl]pentanoate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 (RS)-4-(2-methylphenyl)-5-oxo-5-[3-(pyridin-4-ylmethoxy)phenyl]pentanoic acid
  参考文献：
  名称：

  Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives

  摘要：

  The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ETA receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 mu M, rat aortic ETAR). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 < 0.1 mu M with > 300-fold selectivity for the ETA receptor over the ETB receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.

  DOI：

  10.1016/s0223-5234(97)84014-7
• 作为产物：
  描述：

  3-氰基苯酚 在 palladium on activated charcoal 盐酸 、 potassium tert-butylate 、 氢气 、 碘 、 sodium hydride 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 乙酸甲酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 Methyl 4-(2-methylphenyl)-5-oxo-5-[3-(pyridin-4-ylmethoxy)phenyl]pentanoate
  参考文献：
  名称：

  Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives

  摘要：

  The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ETA receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 mu M, rat aortic ETAR). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 < 0.1 mu M with > 300-fold selectivity for the ETA receptor over the ETB receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.

  DOI：

  10.1016/s0223-5234(97)84014-7

文献信息

• SUBSTITUTED PHENYL COMPOUNDS
  申请人：RHONE-POULENC RORER LIMITED

  公开号：EP0728128B1

  公开（公告）日：1998-09-16