3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylic acid methyl ester | 226916-17-2

• 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: 3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylic acid methyl ester
• 英文别名: (E)-Methyl 3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylate；methyl (E)-3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)prop-2-enoate
• CAS: 226916-17-2
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: AXFWOFLOOPUESJ-SNAWJCMRSA-N

物化性质

• 沸点：
  338.9±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylic acid methyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 (E)-3-(1,4-二噁螺[4.5]-7-癸基-7-基)丙烯酸
  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：

  3-溴-3-环己烯酮缩乙二醇 、 丙烯酸甲酯（MA） 在 bis-triphenylphosphine-palladium(II) chloride 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以71%的产率得到3-(1,4-dioxaspiro[4.5]dec-7-en-7-yl)acrylic acid methyl ester
  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
• WO2006/76565
  申请人：——

  公开号：——

  公开（公告）日：——
• Metabolism-Based Identification of a Potent Thrombin Receptor Antagonist
  作者：Martin C. Clasby、Samuel Chackalamannil、Michael Czarniecki、Dario Doller、Keith Eagen、William Greenlee、Grace Kao、Yan Lin、Hsingan Tsai、Yan Xia、Ho-Sam Ahn、Jacqueline Agans-Fantuzzi、George Boykow、Madhu Chintala、Carolyn Foster、April Smith-Torhan、Kevin Alton、Matthew Bryant、Yunsheng Hsieh、Janice Lau、Jairam Palamanda

  DOI：10.1021/jm061043e

  日期：2007.1.1

  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.