3-(3-cyanophenyl)-5-(carbomethoxymethyl)isoxazoline-5-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3-cyanophenyl)-5-(carbomethoxymethyl)isoxazoline-5-carboxylic acid
• 英文别名: 3-(3-cyanophenyl)-5-(2-methoxy-2-oxoethyl)-4H-1,2-oxazole-5-carboxylic acid
• 化学式: C₁₄H₁₂N₂O₅
• 分子量: 288.26
• InChiKey: IWBWYRGTFPEIMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(3-cyanophenyl)-5-(carbomethoxymethyl)isoxazoline-5-carboxylic acid 在 氯化亚砜 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.0h， 生成 3-(3-cyanophenyl)-5-N-[2'-aminosulfonyl-[1,1']-biphenyl-4-yl]aminocarbonyl-5-carbomethoxy methyl-isoxazoline
  参考文献：
  名称：

  Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 1

  摘要：

  Thrombosis is a major cause of mortality in the industrialized world. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), the enzyme directly responsible for protbrombin activation. We report a series of novel biaryl-substituted isoxazoline derivatives in which the biaryl moiety was designed to interact with the S-4 aryl-binding domain of the FXa active site. Several of the compounds herein have low nanomolar affinity for FXa, have good in vitro selectivity for FXa, and show potent antithrombotic efficacy in vivo, The three most potent compounds (33, 35, and 37) have inhibition constants for human FXa of 3.9, 2.3, and 0.83 nM, respectively, and ID50's ranging from 0.15 to 0.26 mu mol/kg/h in the rabbit arterio-venous thrombosis model.

  DOI：

  10.1021/jm980405i
• 作为产物：
  描述：

  衣康酸单甲酯 在 sodium hypochlorite 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 3-(3-cyanophenyl)-5-(carbomethoxymethyl)isoxazoline-5-carboxylic acid
  参考文献：
  名称：

  Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 1

  摘要：

  Thrombosis is a major cause of mortality in the industrialized world. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), the enzyme directly responsible for protbrombin activation. We report a series of novel biaryl-substituted isoxazoline derivatives in which the biaryl moiety was designed to interact with the S-4 aryl-binding domain of the FXa active site. Several of the compounds herein have low nanomolar affinity for FXa, have good in vitro selectivity for FXa, and show potent antithrombotic efficacy in vivo, The three most potent compounds (33, 35, and 37) have inhibition constants for human FXa of 3.9, 2.3, and 0.83 nM, respectively, and ID50's ranging from 0.15 to 0.26 mu mol/kg/h in the rabbit arterio-venous thrombosis model.

  DOI：

  10.1021/jm980405i

文献信息

• [EN] ISOXAZOLINE, ISOTHIAZOLINE AND PYRAZOLINE FACTOR Xa INHIBITORS<br/>[FR] ISOXAZOLINE, ISOTHIAZOLINE ET PYRAZOLINE INHIBITEURS DU FACTEUR Xa
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1997023212A1

  公开（公告）日：1997-07-03

  (EN) Isoxazolines, isothiazolines and pyrazolines which are inhibitors of Factor Xa, pharmaceutical compositions containing these compounds, and methods of using these compounds as anticoagulant agents for treatment and prevention of thromboembolic disorders. The compounds can be represented by formula (I) where X is O, S or NR15.(FR) L'invention porte sur des isoxazolines, des isothiazolines ainsi que des pyrazolines, agents inhibiteurs du facteur Xa, sur des compositions pharmaceutiques contenant ces composés ainsi que sur des méthodes d'utilisation de ces composés en tant qu'agents anticoagulants pour le traitement et la prévention de troubles thrombo-emboliques. Ces composés peuvent être représentés par la formule (I) dans laquelle X représente O, S ou NR15.

  （中）Isoxazolines、isothiazolines和pyrazolines是Factor Xa的抑制剂，含有这些化合物的药物组合物以及使用这些化合物作为抗凝血剂治疗和预防血栓栓塞疾病的方法。这些化合物可以用公式（I）表示，其中X为O、S或NR15。
• ISOXAZOLINE, ISOTHIAZOLINE AND PYRAZOLINE FACTOR Xa INHIBITORS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP0874629B1

  公开（公告）日：2004-05-19
• EP0874629A4
  申请人：——

  公开号：EP0874629A4

  公开（公告）日：1999-08-04
• US5939418A
  申请人：——

  公开号：US5939418A

  公开（公告）日：1999-08-17