3-(3-cyanophenyl)-5-N-[2'-aminosulfonyl-[1,1']-biphenyl-4-yl]aminocarbonyl-5-carbomethoxy methyl-isoxazoline | 193006-36-9

• 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-N-[2'-aminosulfonyl-[1,1']-biphenyl-4-yl]aminocarbonyl-5-carbomethoxy methyl-isoxazoline
• 英文别名: methyl 2-[3-(3-cyanophenyl)-5-[[4-(2-sulfamoylphenyl)phenyl]carbamoyl]-4H-1,2-oxazol-5-yl]acetate
• CAS: 193006-36-9
• 化学式: C₂₆H₂₂N₄O₆S
• 分子量: 518.55
• InChiKey: ZCSGALSQYYRSBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  169
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-(3-cyanophenyl)-5-N-[2'-aminosulfonyl-[1,1']-biphenyl-4-yl]aminocarbonyl-5-carbomethoxy methyl-isoxazoline 在 盐酸 、 ammonium acetate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 24.0h， 生成 5-isoxazoleacetic acid, 3-<3-(aminoiminomethyl)phenyl>-5-<<<2'-(aminosulfonyl)<1,1'-biphenyl>-4-yl>amino>carbonyl>-4,5-dihydro-, methyl ester
  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：

  2-(4-氨基苯基)-N-叔丁基苯磺酰胺 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 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

文献信息

• 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。
• 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
• Design and Synthesis of Isoxazoline Derivatives as Factor Xa Inhibitors. 1
  作者：Mimi L. Quan、Ann Y. Liauw、Christopher D. Ellis、James R. Pruitt、David J. Carini、Lori L. Bostrom、Peggy P. Huang、Kimberly Harrison、Robert M. Knabb、Martin J. Thoolen、Pancras C. Wong、Ruth R. Wexler

  DOI：10.1021/jm980405i

  日期：1999.7.1

  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.