2,3-dichlorothiophene-5-sulfonic acid [(2E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]amide | 882999-52-2

• 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: 2,3-dichlorothiophene-5-sulfonic acid [(2E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]amide
• 英文别名: 4,5-Dichloro-thiophene-2-sulfonic acid [(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)-acryloyl]-amide；4,5-dichlorothiophene-2-sulfonic acid [(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)-acryloyl]-amide；4,5-dichlorothiophene-2-sulfonic acid [(E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)-acryloyl]amide；(E)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-3-(5-fluoro-3-methyl-1H-indol-7-yl)prop-2-enamide
• CAS: 882999-52-2
• 化学式: C₁₆H₁₁Cl₂FN₂O₃S₂
• 分子量: 433.311
• InChiKey: LGCURHNHKIVNBX-NSCUHMNNSA-N

物化性质

• 密度：
  1.611±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 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：
  116
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-dichlorothiophene-5-sulfonic acid [(2E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]amide 、 4-氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以57%的产率得到4,5-dichlorothiophene-2-sulfonic acid {2-[3-(naphthalene-2-carbonyl)-1H-indol-4-yloxy]acetyl}amide
  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：

  2-溴-4-氟-1-硝基苯 在 4-二甲氨基吡啶 、 水 、 palladium diacetate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 2,3-dichlorothiophene-5-sulfonic acid [(2E)-3-(5-fluoro-3-methyl-1H-indol-7-yl)acryloyl]amide
  参考文献：
  名称：

  Development of a Scalable Process for DG-041, a Potent EP₃ Receptor Antagonist, via Tandem Heck Reactions

  摘要：

  DG-041 is a small molecule antagonist of the EP3 receptor for prostaglandin E-2 that is in clinical development for treatment of peripheral artery disease (PAD). Originally produced using a six-step synthetic procedure, process optimization led to development of a four-step sequence that is readily scalable. The key step in the optimized sequence contains two sequential Heck reactions, involving an intramolecular Heck cyclization followed by an intermolecular Heck coupling, performed in one pot to produce a highly substituted indole core.

  DOI：

  10.1021/op700107h

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：
• PROCESS FOR PREPARING 7-(ACRYLOYL)INDOLES
  申请人：Singh Jasbir

  公开号：US20070270594A1

  公开（公告）日：2007-11-22

  The present invention involves a process for preparing substituted indoles, such as DTSI involving two sequential cross-coupling reactions.

  本发明涉及一种制备取代吲哚的方法，例如DTSI，包括两个连续的交叉偶联反应。
• 7-(ACRYLOYL) INDOLE COMPOSITIONS AND METHODS OF MAKING AND USING SAME
  申请人：Singh Jasbir

  公开号：US20080125477A1

  公开（公告）日：2008-05-29

  The present invention is directed to pharmaceutical compositions of 7-(acryloyl)indoles, such as 4,5 -Dichloro-thiophene-2-sulfonic acid [(E)-3-[1-(2,4-dichlorophenylmethyl)-5-fluoro-3-methyl-1H-indol-7-yl]-acryloyl]amide (DTSI), having a structure shown below. The invention is also directed to methods of treatment utilizing formulations of the DTSI and processes of preparation of the formulations.

  本发明涉及7-(丙烯酰基)吲哚的药物组成物，例如4,5-二氯噻吩-2-磺酸[(E)-3-[1-(2,4-二氯苯甲基)-5-氟-3-甲基-1H-吲哚-7-基]-丙烯酰基]酰胺(DTSI)，其结构如下所示。本发明还涉及利用DTSI制剂的治疗方法以及制备制剂的过程。
• Process for preparing 7-(acryloyl)indoles
  申请人：deCODE Genetics, ehf.

  公开号：US07579483B2

  公开（公告）日：2009-08-25

  The present invention involves a process for preparing substituted indoles, such as DTSI involving two sequential cross-coupling reactions.

  本发明涉及一种制备取代吲哚的方法，例如DTSI，包括两个连续的交叉偶联反应。
• WO2007/137040
  申请人：——

  公开号：——

  公开（公告）日：——