ethyl 7-[(tert-butoxycarbonyl)amino]-2-(sulfanylmethyl)-heptanoate | 1394345-63-1

• 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: ethyl 7-[(tert-butoxycarbonyl)amino]-2-(sulfanylmethyl)-heptanoate
• 英文别名: Ethyl 7-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(sulfanylmethyl)heptanoate；ethyl 7-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(sulfanylmethyl)heptanoate
• CAS: 1394345-63-1
• 化学式: C₁₅H₂₉NO₄S
• 分子量: 319.466
• InChiKey: KOMKSCPVHHAMMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 7-[(tert-butoxycarbonyl)amino]-2-(sulfanylmethyl)-heptanoate 、 三氟乙酸 以 水 为溶剂， 反应 1.0h， 以100%的产率得到ethyl 7-amino-2-(sulfanylmethyl)heptanoate trifluoroacetate
  参考文献：
  名称：

  Design and Characterization of a Selenium-Containing Inhibitor of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa), a Zinc-Containing Metalloprotease

  摘要：

  Available therapies for thromboembolic disorders include thrombolytics, anticoagulants, and antiplatelets, but these are associated with complications such as bleeding. To develop an alternative drug which is clinically safe, we focused on activated thrombin-activatable fibrinolysis inhibitor (TAFIa) as the target molecule. TAFIa is a zinc-containing carboxypeptidase that significantly inhibits fibrinolysis. Here we designed and synthesized selenium-containing compounds 5-13 to discover novel TAFIa inhibitors having a superior zinc-coordinating group. Compounds 5-13 significantly inhibited TAFIa activity (IC50 2.2 x 10(-12) M - 2.6 x 10(-6) M). We found that selenol is a better functional group than thiol for coordinating to zinc at the active site of TAFIa. Furthermore, compound 12, which has an amino-chloro-pyridine ring, was found to be a potent and selective TAFIa inhibitor that lacks carboxypeptidase N inhibitory activity. Therefore, compound 12 is a promising candidate for the treatment of thromboembolic disorders. This is the first report of a selenium-containing inhibitor for TAFIa.

  DOI：

  10.1021/jm300735t
• 作为产物：
  描述：

  5-boc-氨基戊基甲烷磺酸酯 在 聚合甲醛 、 sodium ethanolate 、 sodium acetate 、 二乙胺 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 107.17h， 生成 ethyl 7-[(tert-butoxycarbonyl)amino]-2-(sulfanylmethyl)-heptanoate
  参考文献：
  名称：

  Design and Characterization of a Selenium-Containing Inhibitor of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa), a Zinc-Containing Metalloprotease

  摘要：

  Available therapies for thromboembolic disorders include thrombolytics, anticoagulants, and antiplatelets, but these are associated with complications such as bleeding. To develop an alternative drug which is clinically safe, we focused on activated thrombin-activatable fibrinolysis inhibitor (TAFIa) as the target molecule. TAFIa is a zinc-containing carboxypeptidase that significantly inhibits fibrinolysis. Here we designed and synthesized selenium-containing compounds 5-13 to discover novel TAFIa inhibitors having a superior zinc-coordinating group. Compounds 5-13 significantly inhibited TAFIa activity (IC50 2.2 x 10(-12) M - 2.6 x 10(-6) M). We found that selenol is a better functional group than thiol for coordinating to zinc at the active site of TAFIa. Furthermore, compound 12, which has an amino-chloro-pyridine ring, was found to be a potent and selective TAFIa inhibitor that lacks carboxypeptidase N inhibitory activity. Therefore, compound 12 is a promising candidate for the treatment of thromboembolic disorders. This is the first report of a selenium-containing inhibitor for TAFIa.

  DOI：

  10.1021/jm300735t