N-<2-(S)-<(tert-butoxycarbonyl)amino>-3-phenylpropyl>-methionine methyl ester | 158861-43-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-<2-(S)-<(tert-butoxycarbonyl)amino>-3-phenylpropyl>-methionine methyl ester
• 英文别名: methyl (2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl]amino]-4-methylsulfanylbutanoate
• CAS: 158861-43-9
• 化学式: C₂₀H₃₂N₂O₄S
• 分子量: 396.551
• InChiKey: TWBPECORXBLXGT-IRXDYDNUSA-N

物化性质

• 沸点：
  526.9±50.0 °C(predicted)
• 密度：
  1.102±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<2-(S)-<(tert-butoxycarbonyl)amino>-3-phenylpropyl>-methionine methyl ester 在 N-甲基吗啉 、 盐酸 、 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 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.5h， 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-Boc-L-苯丙氨醛 、 L-蛋氨酸甲酯盐酸盐 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以73%的产率得到N-<2-(S)-<(tert-butoxycarbonyl)amino>-3-phenylpropyl>-methionine methyl ester
  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

文献信息

• Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase
  作者：Samuel L. Graham、S. Jane deSolms、Elizabeth A. Giuliani、Nancy E. Kohl、Scott D. Mosser、Allen I. Oliff、David L. Pompliano、Elaine Rands、Michael J. Breslin

  DOI：10.1021/jm00032a004

  日期：1994.3

  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.