3-(3-cyanophenyl)-5-carbomethoxy-5-(1H-tetrazol-1-ylmethyl)isoxazoline | 193006-39-2

• 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-carbomethoxy-5-(1H-tetrazol-1-ylmethyl)isoxazoline
• 英文别名: 3-(3-cyanophenyl)-5-carbomethoxy-5-(tetrazol-1-yl)methyl-isoxazoline；methyl 3-(3-cyanophenyl)-5-(tetrazol-1-ylmethyl)-4H-1,2-oxazole-5-carboxylate
• CAS: 193006-39-2
• 化学式: C₁₄H₁₂N₆O₃
• 分子量: 312.288
• InChiKey: MNACNUPFHCZKDF-UHFFFAOYSA-N

物化性质

• 沸点：
  504.0±60.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(3-cyanophenyl)-5-carbomethoxy-5-(1H-tetrazol-1-ylmethyl)isoxazoline 在 lithium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.5h， 生成 N-[5-[2-(tert-butylsulfamoyl)phenyl]pyrimidin-2-yl]-3-(3-cyanophenyl)-5-(tetrazol-1-ylmethyl)-4H-1,2-oxazole-5-carboxamide
  参考文献：
  名称：

  Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 2

  摘要：

  Intravascular clot formation is an important factor in a number of cardiovascular diseases, 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 thrombin activation. Herein we report a series of isoxazoline derivatives which are potent FXa inhibitors. Optimization of the side chain at the quaternary position of the isoxazoline ring led to SK549 which showed subnanomolar FXa potency (K-i 0.52 nM). SK549 shows good selectivity for FXa compared to thrombin and trypsin, potent antithrombotic effect in the rabbit arterio-venous thrombosis model, and improved pharmacokinetics relative to other compounds evaluated from this series.

  DOI：

  10.1021/jm980406a
• 作为产物：
  描述：

  3-氰基苯甲醛肟 、 methyl 2-(1H-tetrazol-ylmethyl)acrylate 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 3-(3-cyanophenyl)-5-carbomethoxy-5-(1H-tetrazol-1-ylmethyl)isoxazoline
  参考文献：
  名称：

  Isoxazoline, isothiazoline and pyrazoline factor Xa inhibitors

  摘要：

  异噁唑啉、异硫噁唑啉和吡唑啉是Xa因子的抑制剂，包含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性疾病的方法。这些化合物可以用下面的公式表示：##STR1##其中X为O、S或NR.sup.15。

  公开号：

  US05939418A1

文献信息

• 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
• US5939418A
  申请人：——

  公开号：US5939418A

  公开（公告）日：1999-08-17
• Isoxazoline, isothiazoline and pyrazoline factor Xa inhibitors
  申请人：The DuPont Merck Pharmaceutical Company

  公开号：US05939418A1

  公开（公告）日：1999-08-17

  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 the formula: ##STR1## where X is O, S or NR.sup.15.

  异噁唑啉、异硫噁唑啉和吡唑啉是Xa因子的抑制剂，包含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性疾病的方法。这些化合物可以用下面的公式表示：##STR1##其中X为O、S或NR.sup.15。
• Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 2
  作者：Mimi L. Quan、Christopher D. Ellis、Ann Y. Liauw、Richard S. Alexander、Robert M. Knabb、Gilbert Lam、Matthew R. Wright、Pancras C. Wong、Ruth R. Wexler

  DOI：10.1021/jm980406a

  日期：1999.7.1

  Intravascular clot formation is an important factor in a number of cardiovascular diseases, 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 thrombin activation. Herein we report a series of isoxazoline derivatives which are potent FXa inhibitors. Optimization of the side chain at the quaternary position of the isoxazoline ring led to SK549 which showed subnanomolar FXa potency (K-i 0.52 nM). SK549 shows good selectivity for FXa compared to thrombin and trypsin, potent antithrombotic effect in the rabbit arterio-venous thrombosis model, and improved pharmacokinetics relative to other compounds evaluated from this series.