3,4-difluoro-N-[(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]benzenesulfonamide | 883000-84-8

• 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: 3,4-difluoro-N-[(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]benzenesulfonamide
• 英文别名: (E)-N-(3,4-difluorophenyl)sulfonyl-3-(5-fluoro-3-methyl-1H-indol-7-yl)prop-2-enamide
• CAS: 883000-84-8
• 化学式: C₁₈H₁₃F₃N₂O₃S
• 分子量: 394.374
• InChiKey: ZDPLRXQLDGCULH-GORDUTHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  87.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (2E)-3-(5-氟-3-甲基-1H-吲哚-7-基)-2-丙烯酸 、 3,4-二氟苯磺酰胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 以41%的产率得到3,4-difluoro-N-[(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]benzenesulfonamide
  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

• Sulfonamide peri-substituted bicyclics for occlusive artery disease
  申请人：Singh Jasbir

  公开号：US20060079520A1

  公开（公告）日：2006-04-13

  Acyl sulfonamide, peri-substituted, fused bicyclic ring compounds useful for the treatment or prophylaxis of a prostaglandin-mediated disease or condition are disclosed. The compounds are of the general formula A representative example is:

  酰基磺酰胺，带有周取代的融合双环环化合物，用于治疗或预防前列腺素介导的疾病或症状。这些化合物的一般公式为 代表性示例是：
• SULFONAMIDE PERI-SUBSTITUTED BICYCLICS FOR OCCLUSIVE ARTERY DISEASE
  申请人：Singh Jasbir

  公开号：US20090291948A1

  公开（公告）日：2009-11-26

  Acyl sulfonamide, peri-substituted, fused bicyclic ring compounds useful for the treatment or prophylaxis of a prostaglandin-mediated disease or condition are disclosed. The compounds are of the general formula A representative example is:

  本发明揭示了用于治疗或预防前列腺素介导的疾病或病状的酰基磺酰胺，周围取代，融合的双环环化合物。这些化合物的一般公式为。其中，代表性的例子为：
• SULFONAMIDE PERT-SUBSTITUTED BICYCLICS FOR OCCLUSIVE ARTERY DISEASE
  申请人：Decode Genetics

  公开号：EP1812388A1

  公开（公告）日：2007-08-01
• US7598397B2
  申请人：——

  公开号：US7598397B2

  公开（公告）日：2009-10-06
• [EN] SULFONAMIDE PERT-SUBSTITUTED BICYCLICS FOR OCCLUSIVE ARTERY DISEASE<br/>[FR] BICYCLIQUES PERI-SUBSTITUES DE SULFONAMIDE POUR MALADIE D'ARTERE OCCLUSE
  申请人：DECODE GENETICS

  公开号：WO2006044000A1

  公开（公告）日：2006-04-27

  [EN] Acyl sulfonamide, peri-substituted, fused bicyclic ring compounds useful for the treatment or prophylaxis of a prostaglandin-mediated disease or condition are disclosed. The compounds are of the general formula (I). A representative example is formula (II):
  [FR] L'invention concerne des composés d'anneau bicyclique fusionné, péri-substitué, d'acylsulfonamide, utilisés dans le traitement ou la prophylaxie d'une maladie ou d'un trouble à médiation de prostaglandine. Les composés présentent la formule générale (I). Un exemple représentatif en est la formule (II):