N-{(E)-3-[1-(3,5-dimethylisoxazol-4-ylmethyl)-5-fluoro-3-methyl-1H-indol-7-yl]acryloyl}-3,4-difluorobenzenesulfonamide | 882998-72-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: N-{(E)-3-[1-(3,5-dimethylisoxazol-4-ylmethyl)-5-fluoro-3-methyl-1H-indol-7-yl]acryloyl}-3,4-difluorobenzenesulfonamide
• 英文别名: (E)-N-(3,4-difluorophenyl)sulfonyl-3-[1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-5-fluoro-3-methylindol-7-yl]prop-2-enamide
• CAS: 882998-72-3
• 化学式: C₂₄H₂₀F₃N₃O₄S
• 分子量: 503.502
• InChiKey: ZERUZZSPUFDMCH-QPJJXVBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(bromomethyl)-3,5-dimethylisoxazole 、 3,4-difluoro-N-[(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]benzenesulfonamide 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以31%的产率得到N-{(E)-3-[1-(3,5-dimethylisoxazol-4-ylmethyl)-5-fluoro-3-methyl-1H-indol-7-yl]acryloyl}-3,4-difluorobenzenesulfonamide
  参考文献：
  名称：

  Structure−Activity Relationship Studies Leading to the Identification of (2E)-3-[l-[(2,4-Dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a Potent and Selective Prostanoid EP3 Receptor Antagonist, as a Novel Antiplatelet Agent That Does Not Prolong Bleeding

  摘要：

  The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged oil a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.

  DOI：

  10.1021/jm9005912

文献信息

• Structure−Activity Relationship Studies Leading to the Identification of (2<i>E</i>)-3-[l-[(2,4-Dichlorophenyl)methyl]-5-fluoro-3-methyl-l<i>H</i>-indol-7-yl]-<i>N</i>-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a Potent and Selective Prostanoid EP3 Receptor Antagonist, as a Novel Antiplatelet Agent That Does Not Prolong Bleeding
  作者：Jasbir Singh、Wayne Zeller、Nian Zhou、Georgeta Hategan、Rama K. Mishra、Alex Polozov、Peng Yu、Emmanuel Onua、Jun Zhang、José L. Ramírez、Gudmundur Sigthorsson、Margret Thorsteinnsdottir、Alex. S. Kiselyov、David E. Zembower、Thorkell Andrésson、Mark E. Gurney

  DOI：10.1021/jm9005912

  日期：2010.1.14

  The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged oil a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.