(2,4-dichlorophenyl)[2-bromo-4-(E-((3-(2-oxopyrrolidin-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide | 280749-30-6

• 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: (2,4-dichlorophenyl)[2-bromo-4-(E-((3-(2-oxopyrrolidin-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide
• 英文别名: 3-[3-Bromo-4-(2,4-dichloro-phenylsulfanyl)-phenyl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-acrylamide；(E)-3-[3-bromo-4-(2,4-dichlorophenyl)sulfanylphenyl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]prop-2-enamide
• CAS: 280749-30-6
• 化学式: C₂₂H₂₁BrCl₂N₂O₂S
• 分子量: 528.297
• InChiKey: NZDSKVKNJZPPBI-WEVVVXLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 (2,4-dichlorophenyl)[2-bromo-4-(E-((3-(2-oxopyrrolidin-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide 在 tris(dibenzylideneacetone)dipalladium (0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 生成 (E)-3-[4-(2,4-Dichloro-phenylsulfanyl)-3-(3-morpholin-4-yl-propylamino)-phenyl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-acrylamide
  参考文献：
  名称：

  Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intracellular Adhesion Molecule-1 Interaction. 1. Identification of an Additional Binding Pocket Based on an Anilino Diaryl Sulfide Lead

  摘要：

  The interaction between leukocyte function-associated antigen-1 (LFA-1), a member of the beta (2)-integrin family of adhesion molecules, and intracellular adhesion molecule ICAM-1 (cd54) is thought to play a critical role in the inflammatory process. On the basis of an anilino diaryl sulfide screening lead 1, in combination with pharmacophore analysis of other screening hits, we have identified an adjacent binding pocket. Subsequently, a p-ethenylcarbonyl linker was discovered to be optimal for accessing this binding site. Solution-phase parallel synthesis enabled rapid optimization of the cinnamides for this pocket. In conjunction with fine-tuning of the diaryl substituents, we discovered a novel series of potent, nonpeptide inhibitors of LFA-1/ICAM-1 interaction, exemplified by A-286982 (28h), which has IC50 values of 44 and 35 nM in an LFA-1/ICAM-1 binding assay and LFA-l-mediated cellular adhesion assay, respectively.

  DOI：

  10.1021/jm0002782
• 作为产物：
  描述：

  (2,4-dichlorophenyl)[2-nitro-4-(E-((3-(2-oxopyrrolidin-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide 在 亚硝酸特丁酯 、 乙醇 、 tin(ll) chloride 、 copper(ll) bromide 作用下， 以 乙腈 为溶剂， 反应 1.5h， 生成 (2,4-dichlorophenyl)[2-bromo-4-(E-((3-(2-oxopyrrolidin-1-yl)propylamino)carbonyl)ethenyl)phenyl]sulfide
  参考文献：
  名称：

  Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intracellular Adhesion Molecule-1 Interaction. 1. Identification of an Additional Binding Pocket Based on an Anilino Diaryl Sulfide Lead

  摘要：

  The interaction between leukocyte function-associated antigen-1 (LFA-1), a member of the beta (2)-integrin family of adhesion molecules, and intracellular adhesion molecule ICAM-1 (cd54) is thought to play a critical role in the inflammatory process. On the basis of an anilino diaryl sulfide screening lead 1, in combination with pharmacophore analysis of other screening hits, we have identified an adjacent binding pocket. Subsequently, a p-ethenylcarbonyl linker was discovered to be optimal for accessing this binding site. Solution-phase parallel synthesis enabled rapid optimization of the cinnamides for this pocket. In conjunction with fine-tuning of the diaryl substituents, we discovered a novel series of potent, nonpeptide inhibitors of LFA-1/ICAM-1 interaction, exemplified by A-286982 (28h), which has IC50 values of 44 and 35 nM in an LFA-1/ICAM-1 binding assay and LFA-l-mediated cellular adhesion assay, respectively.

  DOI：

  10.1021/jm0002782

文献信息

• Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
  申请人：Abbott Laboratories

  公开号：US20040116518A1

  公开（公告）日：2004-06-17

  The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases and cerebral vasospasm, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.

  本发明涉及新型肉桂酰胺化合物，用于治疗炎症和免疫性疾病以及脑血管痉挛，以及含有这些化合物的药物组合物，以及在哺乳动物中抑制炎症或抑制免疫反应的方法。