N-<2(S)-<<(tert-butoxycarbonyl)-S-(triphenylmethyl)cysteinyl>amino>-3-methylpentyl>isoleucylhomoserine lactone | 1026801-45-5

• 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(S)-<<(tert-butoxycarbonyl)-S-(triphenylmethyl)cysteinyl>amino>-3-methylpentyl>isoleucylhomoserine lactone
• 英文别名: tert-butyl N-[(2R)-1-[[(2S)-3-methyl-1-[[(2S)-3-methyl-1-oxo-1-[[(3S)-2-oxooxolan-3-yl]amino]pentan-2-yl]amino]pentan-2-yl]amino]-1-oxo-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 1026801-45-5
• 化学式: C₄₃H₅₈N₄O₆S
• 分子量: 759.023
• InChiKey: WSPJXLVMLBTFDL-STQGQLATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  54
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-<2(S)-<<(tert-butoxycarbonyl)-S-(triphenylmethyl)cysteinyl>amino>-3-methylpentyl>isoleucylhomoserine lactone 在 三乙基硅烷 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-<2(S)-(cysteinylamino)-3-methylpentyl>isoleucylhomoserine
  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：

  2-甲基-2-丙基[(2S,3R)-3-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 盐酸 、 3 A molecular sieve 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 N-<2(S)-<<(tert-butoxycarbonyl)-S-(triphenylmethyl)cysteinyl>amino>-3-methylpentyl>isoleucylhomoserine lactone
  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.