methyl (2S)-2-[[4-(aminomethyl)-2-naphthalen-1-ylbenzoyl]amino]-4-methylpentanoate | 748755-06-8

• 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: methyl (2S)-2-[[4-(aminomethyl)-2-naphthalen-1-ylbenzoyl]amino]-4-methylpentanoate
• CAS: 748755-06-8
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: LMBSOYFDQKHAKA-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[4-(aminomethyl)-2-naphthalen-1-ylbenzoyl]amino]-4-methylpentanoate 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 10.25h， 生成
  参考文献：
  名称：

  Potent, Highly Selective, and Non-Thiol Inhibitors of Protein Geranylgeranyltransferase-I

  摘要：

  The design, synthesis, and biological evaluation of a family of peptidomimetic inhibitors of protein geranylgeranyltransferase-I (PGGTase-I) are reported. The inhibitors are based on the C-terminal CAAL sequence of many geranylgeranylated proteins. Using 2-aryl-4-aminobenzoic acid derivatives as mimetics for the central dipeptide (AA), we have attached a series of imidazole and pyridine derivatives to the N-terminus as cysteine replacements. These non-thiol-containing peptidomimetics show exceptional selectivity for PGGTase-I over the closely related enzyme protein farnesyltransferase (PFTase). This selectivity is retained in whole cells where the inhibitors were shown to block the geranylgeranylation of Rap-1A without affecting the farnesylation of small GTP-binding proteins such as Ras.

  DOI：

  10.1021/jm9900873
• 作为产物：
  描述：

  methyl 4-iodo-2-(1-naphthyl)benzoate 在 lithium hydroxide 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 cobalt(II) chloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 23.0h， 生成 methyl (2S)-2-[[4-(aminomethyl)-2-naphthalen-1-ylbenzoyl]amino]-4-methylpentanoate
  参考文献：
  名称：

  Potent, Highly Selective, and Non-Thiol Inhibitors of Protein Geranylgeranyltransferase-I

  摘要：

  The design, synthesis, and biological evaluation of a family of peptidomimetic inhibitors of protein geranylgeranyltransferase-I (PGGTase-I) are reported. The inhibitors are based on the C-terminal CAAL sequence of many geranylgeranylated proteins. Using 2-aryl-4-aminobenzoic acid derivatives as mimetics for the central dipeptide (AA), we have attached a series of imidazole and pyridine derivatives to the N-terminus as cysteine replacements. These non-thiol-containing peptidomimetics show exceptional selectivity for PGGTase-I over the closely related enzyme protein farnesyltransferase (PFTase). This selectivity is retained in whole cells where the inhibitors were shown to block the geranylgeranylation of Rap-1A without affecting the farnesylation of small GTP-binding proteins such as Ras.

  DOI：

  10.1021/jm9900873

文献信息

• Potent, Highly Selective, and Non-Thiol Inhibitors of Protein Geranylgeranyltransferase-I
  作者：Anil Vasudevan、Yimin Qian、Andreas Vogt、Michelle A. Blaskovich、Junko Ohkanda、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1021/jm9900873

  日期：1999.4.22

  The design, synthesis, and biological evaluation of a family of peptidomimetic inhibitors of protein geranylgeranyltransferase-I (PGGTase-I) are reported. The inhibitors are based on the C-terminal CAAL sequence of many geranylgeranylated proteins. Using 2-aryl-4-aminobenzoic acid derivatives as mimetics for the central dipeptide (AA), we have attached a series of imidazole and pyridine derivatives to the N-terminus as cysteine replacements. These non-thiol-containing peptidomimetics show exceptional selectivity for PGGTase-I over the closely related enzyme protein farnesyltransferase (PFTase). This selectivity is retained in whole cells where the inhibitors were shown to block the geranylgeranylation of Rap-1A without affecting the farnesylation of small GTP-binding proteins such as Ras.