N-[3-benzoyl-4-[2-(4-nitrophenyl)acetylamino]phenyl]-N^α-tert-butyloxycarbonyl-S-tritylcysteinamide | 366456-90-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-[3-benzoyl-4-[2-(4-nitrophenyl)acetylamino]phenyl]-N^α-tert-butyloxycarbonyl-S-tritylcysteinamide
• 英文别名: tert-butyl N-[(2R)-1-[3-benzoyl-4-[[2-(4-nitrophenyl)acetyl]amino]anilino]-1-oxo-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 366456-90-8
• 化学式: C₄₈H₄₄N₄O₇S
• 分子量: 820.966
• InChiKey: ZIQBXUIRMDPEFR-WBCKFURZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  60
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  185
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[3-benzoyl-4-[2-(4-nitrophenyl)acetylamino]phenyl]-N^α-tert-butyloxycarbonyl-S-tritylcysteinamide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[3-benzoyl-4-[2-(4-nitrophenyl)acetylamino]phenyl]cysteinamide
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Structure−Activity Relationship of Benzophenone-Based CAAX-Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  Because of the involvement of farnesylated proteins in oncogenesis, inhibition of the protein-modifying enzyme farnesyltransferase is considered a major emerging strategy in cancer therapy. Here, we describe the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. 4 ' -Methyl, 4 ' -chloro, 4 ' -bromo, and 4 ' -nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone core structure yield farnesyltransferase inhibitors active in the nanomolar range. Using diphenylacetic acid in this position further improves activity. SEAL superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX-peptide shows a markedly good resemblance of the molecular properties of the peptide. FlexX docking of 12a confirms the good fit of the molecule into the peptide binding site of farnesyltransferase. The novel benzophenone-based AAX-peptidomimetic substructure described here will be useful for the design of some novel types of farnesyltransferase inhibitors.

  DOI：

  10.1021/jm010872r
• 作为产物：
  描述：

  2-氨基-5-硝基二苯甲酮 在 吡啶 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 N-[3-benzoyl-4-[2-(4-nitrophenyl)acetylamino]phenyl]-N^α-tert-butyloxycarbonyl-S-tritylcysteinamide
  参考文献：
  名称：

  Synthesis, Molecular Modeling, and Structure−Activity Relationship of Benzophenone-Based CAAX-Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  Because of the involvement of farnesylated proteins in oncogenesis, inhibition of the protein-modifying enzyme farnesyltransferase is considered a major emerging strategy in cancer therapy. Here, we describe the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. 4 ' -Methyl, 4 ' -chloro, 4 ' -bromo, and 4 ' -nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone core structure yield farnesyltransferase inhibitors active in the nanomolar range. Using diphenylacetic acid in this position further improves activity. SEAL superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX-peptide shows a markedly good resemblance of the molecular properties of the peptide. FlexX docking of 12a confirms the good fit of the molecule into the peptide binding site of farnesyltransferase. The novel benzophenone-based AAX-peptidomimetic substructure described here will be useful for the design of some novel types of farnesyltransferase inhibitors.

  DOI：

  10.1021/jm010872r