N-[5-[2-(tert-butylsulfamoyl)phenyl]pyrimidin-2-yl]-3-(3-cyanophenyl)-5-(ethylsulfonylmethyl)-4H-1,2-oxazole-5-carboxamide | 1026305-71-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-[5-[2-(tert-butylsulfamoyl)phenyl]pyrimidin-2-yl]-3-(3-cyanophenyl)-5-(ethylsulfonylmethyl)-4H-1,2-oxazole-5-carboxamide
• CAS: 1026305-71-4
• 化学式: C₂₈H₃₀N₆O₆S₂
• 分子量: 610.715
• InChiKey: QECFGYGOYISDGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  197
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-[5-[2-(tert-butylsulfamoyl)phenyl]pyrimidin-2-yl]-3-(3-cyanophenyl)-5-(ethylsulfonylmethyl)-4H-1,2-oxazole-5-carboxamide 在 盐酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 3-{5-Ethanesulfonylmethyl-5-[5-(2-sulfamoyl-phenyl)-pyrimidin-2-ylcarbamoyl]-4,5-dihydro-isoxazol-3-yl}-benzimidic acid methyl ester
  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-cyano-N-hydroxybenzimidoyl chloride 在 Oxone 、 lithium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 N-[5-[2-(tert-butylsulfamoyl)phenyl]pyrimidin-2-yl]-3-(3-cyanophenyl)-5-(ethylsulfonylmethyl)-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

文献信息

• 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.