3-[7-(4-Carbamimidoyl-phenylethynyl)-1-methyl-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-propionic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-[7-(4-Carbamimidoyl-phenylethynyl)-1-methyl-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-propionic acid
• 英文别名: 3-[7-[2-(4-carbamimidoylphenyl)ethynyl]-1-methyl-2,5-dioxo-3H-1,4-benzodiazepin-4-yl]propanoic acid
• 化学式: C₂₂H₂₀N₄O₄
• 分子量: 404.425
• InChiKey: ZGISQAAIGWPLSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-甲基蒽 在 吡啶 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 copper(l) iodide 、 硫化氢 、 ammonium acetate 、 一氯化碘 、 potassium carbonate 、 三乙胺 、 碘甲烷 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[7-(4-Carbamimidoyl-phenylethynyl)-1-methyl-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-propionic acid
  参考文献：
  名称：

  From Peptide to Non-Peptide. 2. The de Novo Design of Potent, Non-peptidal Inhibitors of Platelet Aggregation Based on a Benzodiazepinedione Scaffold

  摘要：

  Earlier studies of peptides containing the arginine-glycine-aspartic acid (RGD) sequence led to the development of a structural model describing the three-dimensional presentation required for RGD-mediated inhibition of glycoprotein IIbIIIa/fibrinogen binding. We describe here the use of that structural model to design a rigid, non-peptidal lead series that reproduces the topography of the peptide backbone using a benzodiazepinedione scaffold. This scaffold is used to synthesize novel molecules which are highly potent inhibitors of platelet aggregation and which possess improved bioavailability. The importance of shape as a design criterion is demonstrated by constructing molecules that present alternative topographies; these molecules are shown to be significantly less potent.

  DOI：

  10.1021/ja00091a008

文献信息

• NONPEPTIDYL INTEGRIN INHIBITORS HAVING SPECIFICITY FOR THE GPII b?III a? RECEPTOR
  申请人：GENENTECH, INC.

  公开号：EP0610334A1

  公开（公告）日：1994-08-17
• US5674863A
  申请人：——

  公开号：US5674863A

  公开（公告）日：1997-10-07
• US5674865A
  申请人：——

  公开号：US5674865A

  公开（公告）日：1997-10-07
• From Peptide to Non-Peptide. 2. The de Novo Design of Potent, Non-peptidal Inhibitors of Platelet Aggregation Based on a Benzodiazepinedione Scaffold
  作者：Robert S. McDowell、Brent K. Blackburn、Thomas R. Gadek、Lawrence R. McGee、Thomas Rawson、Mark E. Reynolds、Kirk D. Robarge、Todd C. Somers、Eugene D. Thorsett

  DOI：10.1021/ja00091a008

  日期：1994.6

  Earlier studies of peptides containing the arginine-glycine-aspartic acid (RGD) sequence led to the development of a structural model describing the three-dimensional presentation required for RGD-mediated inhibition of glycoprotein IIbIIIa/fibrinogen binding. We describe here the use of that structural model to design a rigid, non-peptidal lead series that reproduces the topography of the peptide backbone using a benzodiazepinedione scaffold. This scaffold is used to synthesize novel molecules which are highly potent inhibitors of platelet aggregation and which possess improved bioavailability. The importance of shape as a design criterion is demonstrated by constructing molecules that present alternative topographies; these molecules are shown to be significantly less potent.