N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>isoleucine

• 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-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>isoleucine
• 英文别名: (2S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentanoic acid
• 化学式: C₃₃H₄₂N₂O₄S
• 分子量: 562.773
• InChiKey: XBZXQYCCQILVRY-QAMDSPJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>isoleucine 在 N-甲基吗啉 、 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成
  参考文献：
  名称：

  Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase

  摘要：

  Inhibitors of Ras farnesyl-protein transferase are described. These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Deletion of the carbonyl groups between the first two residues of the tetrapeptides either preserves or improves activity, depending on the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 = 5 nM) is Cys[PSICH2NH]Ile[PSICH2NH]Phe-Met(3). To obtain compounds able to suppress Ras farnesylation in cell culture, further structural modification to include a homoserine lactone prodrug was required. Compound 18(Cys[PSICH2NH]Ile[PSICH2NH]Ile-homoserine lactone)reduced the extent of Ras farnesylation by 50 % in NIH3T3 fibroblasts in culture at a concentration of 50 muM. Structure-activity studies also led to 12 (Cys[PSICH2NH]Val-Ile-Leu), a potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl protein transferase.

  DOI：

  10.1021/jm00032a004
• 作为产物：
  描述：

  N-叔丁氧羰基-S-三苯甲基-L-半胱氨酸 在 N-甲基哌啶 、 lithium aluminium tetrahydride 、 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 72.08h， 生成 N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>isoleucine
  参考文献：
  名称：

  Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase

  摘要：

  Inhibitors of Ras farnesyl-protein transferase are described. These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Deletion of the carbonyl groups between the first two residues of the tetrapeptides either preserves or improves activity, depending on the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 = 5 nM) is Cys[PSICH2NH]Ile[PSICH2NH]Phe-Met(3). To obtain compounds able to suppress Ras farnesylation in cell culture, further structural modification to include a homoserine lactone prodrug was required. Compound 18(Cys[PSICH2NH]Ile[PSICH2NH]Ile-homoserine lactone)reduced the extent of Ras farnesylation by 50 % in NIH3T3 fibroblasts in culture at a concentration of 50 muM. Structure-activity studies also led to 12 (Cys[PSICH2NH]Val-Ile-Leu), a potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl protein transferase.

  DOI：

  10.1021/jm00032a004