(E)-3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)prop-2-enoic acid | 226915-97-5

• 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: (E)-3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)prop-2-enoic acid
• CAS: 226915-97-5
• 化学式: C₁₁H₁₄O₄
• 分子量: 210.23
• InChiKey: KHGAVYMVFVJMDJ-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)prop-2-enoic acid 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 4-吡咯烷基吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 xylene 为溶剂， 215.0 ℃ 、101.33 kPa 条件下， 生成
  参考文献：
  名称：

  Metabolism-Based Identification of a Potent Thrombin Receptor Antagonist

  摘要：

  The metabolism of our prototypical thrombin receptor antagonist 1, K-i = 2.7 nM, was studied and three major metabolites (2,4, and 5) were found. The structures of the metabolites were verified independently by synthesis. Compound 4 was shown to be a potent antagonist of the thrombin receptor with a K-i = 11 nM. Additionally, compound 4 showed a 3-fold improvement in potency with respect to 1 in an agonist-induced ex-vivo platelet aggregation assay in cynomolgus monkeys after oral administration; this activity was sustained with 60% inhibition observed at 24 h post-dose. Compound 4 was highly active in functional assays and showed excellent oral bioavailability in rats and monkeys. Compound 4 showed a superior rat enzyme induction profile relative to compound 1, allowing it to replace compound 1 as a development candidate.

  DOI：

  10.1021/jm061043e
• 作为产物：
  描述：

  1,4-二氧杂螺[4.5]癸-7-烯-8-基三氟甲磺酸酯 在 bis-triphenylphosphine-palladium(II) chloride sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (E)-3-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)prop-2-enoic acid
  参考文献：
  名称：

  Metabolism-Based Identification of a Potent Thrombin Receptor Antagonist

  摘要：

  The metabolism of our prototypical thrombin receptor antagonist 1, K-i = 2.7 nM, was studied and three major metabolites (2,4, and 5) were found. The structures of the metabolites were verified independently by synthesis. Compound 4 was shown to be a potent antagonist of the thrombin receptor with a K-i = 11 nM. Additionally, compound 4 showed a 3-fold improvement in potency with respect to 1 in an agonist-induced ex-vivo platelet aggregation assay in cynomolgus monkeys after oral administration; this activity was sustained with 60% inhibition observed at 24 h post-dose. Compound 4 was highly active in functional assays and showed excellent oral bioavailability in rats and monkeys. Compound 4 showed a superior rat enzyme induction profile relative to compound 1, allowing it to replace compound 1 as a development candidate.

  DOI：

  10.1021/jm061043e

文献信息

• THROMBIN RECEPTOR ANTAGONISTS
  申请人：SCHERING CORPORATION

  公开号：EP1036072B1

  公开（公告）日：2004-05-06