ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-4,9,11b-trimethyl-8-(((tetrahydro-2H-pyran-4-yl)oxy)imino)tetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-4,9,11b-trimethyl-8-(((tetrahydro-2H-pyran-4-yl)oxy)imino)tetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
• 英文别名: ethyl (1R,4S,5R,9S,10R,13S,14E)-5,9,13-trimethyl-14-(oxan-4-yloxyimino)tetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate
• 化学式: C₂₇H₄₃NO₄
• 分子量: 445.643
• InChiKey: QQRAFSJREPNVPV-UZDFUANBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  57.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异甜菊醇 在 盐酸羟胺 、 sodium hydride 、 碳酸氢钠 、 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 19.0h， 生成 ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-4,9,11b-trimethyl-8-(((tetrahydro-2H-pyran-4-yl)oxy)imino)tetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
  参考文献：
  名称：

  Discovery of novel, potent, isosteviol-based antithrombotic agents

  摘要：

  Thrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (K-i = 0.015 mu M) against a panel of serine proteases and showed excellent anticoagulant activity (significant prolongation of ex vivo PT and aPTT over the vehicle, p < 0.01). 6k also significantly inhibited ADP-induced platelet aggregation in rats relative to the vehicle (p < 0.01). Furthermore, 6k exhibited potent ex vivo and in vivo antithrombotic activity in rats relative to the vehicle (p < 0.01 and p < 0.0001, respectively). Novel structure 6k, with potent antithrombotic activity, is expected to lead a promising approach for the development of antithrombotic agents. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111722

文献信息

• Discovery of novel, potent, isosteviol-based antithrombotic agents
  作者：Peng Chen、Dianwen Zhang、Meng Li、Qiong Wu、Yuko P.Y. Lam、Yan Guo、Chen Chen、Nan Bai、Shipra Malhotra、Wei Li、Peter B. O'Connor、Hongzheng Fu

  DOI：10.1016/j.ejmech.2019.111722

  日期：2019.12

  Thrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (K-i = 0.015 mu M) against a panel of serine proteases and showed excellent anticoagulant activity (significant prolongation of ex vivo PT and aPTT over the vehicle, p < 0.01). 6k also significantly inhibited ADP-induced platelet aggregation in rats relative to the vehicle (p < 0.01). Furthermore, 6k exhibited potent ex vivo and in vivo antithrombotic activity in rats relative to the vehicle (p < 0.01 and p < 0.0001, respectively). Novel structure 6k, with potent antithrombotic activity, is expected to lead a promising approach for the development of antithrombotic agents. (C) 2019 Elsevier Masson SAS. All rights reserved.