(+/-)-5-(3-benzyloxyphenyl)-5-oxo-4-cyclopentylpentanoic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+/-)-5-(3-benzyloxyphenyl)-5-oxo-4-cyclopentylpentanoic acid
• 英文别名: 4-Cyclopentyl-5-oxo-5-(3-phenylmethoxyphenyl)pentanoic acid
• 化学式: C₂₃H₂₆O₄
• 分子量: 366.457
• InChiKey: JGBBDMRNYDBKOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氰基苯酚 在 盐酸 、 sodium hydroxide 、 四丁基氟化铵 、 碘 、 sodium hydride 、 magnesium 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.0h， 生成 (+/-)-5-(3-benzyloxyphenyl)-5-oxo-4-cyclopentylpentanoic 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

文献信息

• Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives
  作者：P.C. Astles、T.J. Brown、N.V. Harris、M.F. Harper、C McCarthy、B Porter、C Smith、R.J.A. Walsh

  DOI：10.1016/s0223-5234(97)84014-7

  日期：1997.6

  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.