2-acetoxy-4-(thien-3-yl)methoxybenxonitrile | 263411-26-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2-acetoxy-4-(thien-3-yl)methoxybenxonitrile
• CAS: 263411-26-3
• 化学式: C₁₄H₁₁NO₃S
• 分子量: 273.312
• InChiKey: JWMGHMCNZYDWOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  59.32
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-acetoxy-4-(thien-3-yl)methoxybenxonitrile 在 甲醇 、 sodium hydroxide 、 sodium hydride 、 potassium carbonate 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 3.67h， 生成 (RS)-[2-cyano-5-(thien-3-ylmethoxy)phenoxy]-(2-methyl-phenyl)acetic acid
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b
• 作为产物：
  描述：

  乙酸酐 、 2-hydroxy-4-(thien-3-yl)methoxybenzaldehyde oxime 在 sodium acetate 作用下， 反应 1.5h， 生成 2-acetoxy-4-(thien-3-yl)methoxybenxonitrile
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b