4-{1-[(1-methoxycarbonyl-2-phenylethylcarbamoyl)methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl}-imidazole-1-carboxylic acid tert-butyl ester | 847665-22-9

• 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: 4-{1-[(1-methoxycarbonyl-2-phenylethylcarbamoyl)methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl}-imidazole-1-carboxylic acid tert-butyl ester
• CAS: 847665-22-9
• 化学式: C₂₉H₃₁N₅O₇
• 分子量: 561.594
• InChiKey: DQIHFZWXRSZNKI-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  41.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  143.52
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  4-{1-[(1-methoxycarbonyl-2-phenylethylcarbamoyl)methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl}-imidazole-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I

  摘要：

  A series of novel protein geranylgeranyltransferase-I (PGGTase-I) inhibitors based on a benzoyleneurea scaffold has been synthesized. Using a benzoyleneurea scaffold as a mimetic for the central dipeptide (AA), we have developed CAAX peptidomimetic inhibitors that selectively block the activity of PGGTase-I over the closely related enzyme protein farnesyltransferase. In this new class of PGGTase-I inhibitors, compound (6c) with X = L-phenylalanine displayed the highest inhibition activity against PGGTase-I with an IC50 value of 170 nM. The inhibitors described in this study represent novel and promising leads for the development of potent and selective inhibitors of mammalian PGGTase-I for potential application as antitumor agents. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.053
• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 palladium on activated charcoal ammonium sulfate 、 乙醇 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 4.5h， 生成 4-{1-[(1-methoxycarbonyl-2-phenylethylcarbamoyl)methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl}-imidazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I

  摘要：

  A series of novel protein geranylgeranyltransferase-I (PGGTase-I) inhibitors based on a benzoyleneurea scaffold has been synthesized. Using a benzoyleneurea scaffold as a mimetic for the central dipeptide (AA), we have developed CAAX peptidomimetic inhibitors that selectively block the activity of PGGTase-I over the closely related enzyme protein farnesyltransferase. In this new class of PGGTase-I inhibitors, compound (6c) with X = L-phenylalanine displayed the highest inhibition activity against PGGTase-I with an IC50 value of 170 nM. The inhibitors described in this study represent novel and promising leads for the development of potent and selective inhibitors of mammalian PGGTase-I for potential application as antitumor agents. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.053