[3-((2E,6E)-3,7,11-Trimethyl-dodeca-2,6,10-trienyl)-3H-imidazol-4-yl]-acetic acid methyl ester | 220184-41-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [3-((2E,6E)-3,7,11-Trimethyl-dodeca-2,6,10-trienyl)-3H-imidazol-4-yl]-acetic acid methyl ester
• 英文别名: Methyl 1-(3,7,11-trimethyl-2,6,10-dodecatrien-1-yl)-1H-imidazole-5-acetate；methyl 2-[3-(3,7,11-trimethyldodeca-2,6,10-trienyl)imidazol-4-yl]acetate
• CAS: 220184-41-8
• 化学式: C₂₁H₃₂N₂O₂
• 分子量: 344.497
• InChiKey: FHEOVAYUENJSEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [3-((2E,6E)-3,7,11-Trimethyl-dodeca-2,6,10-trienyl)-3H-imidazol-4-yl]-acetic acid methyl ester 在 lithium hydroxide 、 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(methylsulfanyl)-2(S)-<2-[(3(S)-methyl-2(S)-<2-[3-(3,7,11-trimethyldodeca-2,6,10-trienyl)-3H-imidazol-4-yl]acetylamino>pentyl)naphthalen-1-ylmethylamino]acetylamino>butyric acid
  参考文献：
  名称：

  Design and in Vivo Analysis of Potent Non-Thiol Inhibitors of Farnesyl Protein Transferase

  摘要：

  Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1,5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical. behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

  DOI：

  10.1021/jm990080l
• 作为产物：
  描述：

  在 甲醇 作用下， 生成 [3-((2E,6E)-3,7,11-Trimethyl-dodeca-2,6,10-trienyl)-3H-imidazol-4-yl]-acetic acid methyl ester
  参考文献：
  名称：

  Design and in Vivo Analysis of Potent Non-Thiol Inhibitors of Farnesyl Protein Transferase

  摘要：

  Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1,5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical. behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

  DOI：

  10.1021/jm990080l