N-(geranylgeranyloxy)phthalimide | 175091-94-8

• 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: N-(geranylgeranyloxy)phthalimide
• 英文别名: (E,E,E)-N-(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxy)phthalimide；2-[(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenoxy]isoindole-1,3-dione
• CAS: 175091-94-8
• 化学式: C₂₈H₃₇NO₃
• 分子量: 435.607
• InChiKey: YORVQFRUDPLCOT-HWIYRCFISA-N

物化性质

• 沸点：
  552.1±60.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(geranylgeranyloxy)phthalimide 在 sodium hydroxide 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 42.0h， 生成 monosodium salt of ethyl (E,E,E)-{2-oxo-2-[[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)oxy]amino]ethyl}phosphonate
  参考文献：
  名称：

  Geranylgeranyl Diphosphate-Based Inhibitors of Post-Translational Geranylgeranylation of Cellular Proteins

  摘要：

  A novel series of stable analogs of geranylgeranyl diphosphate (GGdP) are described in which the biologically labile diphosphate moiety of GGdP is replaced by portions that can act as stable isosters. The compounds inhibited the geranylgeranyltransferase activity in whole PC-3 prostate cancer cells, as determined by the inhibition of post-translational isoprenylation of the small GTP-binding protein p21rap 1 and the accumulation of unprocessed p21rap 1 in the cytosolic fraction. However, the compounds did not affect the farnesylation of p21ras, as shown by protein immunoprecipitation after whole cell labeling with [H-3]-(R,S)-mevalonolactone. Despite the absence of effects on post-translational processing of p21ras, these compounds proved to be cytotoxic for prostate cancer cells, with half-maximal inhibition of cell growth obtained in the range 18.5-35.1 mu M. The GGdP analogs described in the this study are novel, non-peptidic inhibitors of geranylgeranylation that may be active as antitumor agents.

  DOI：

  10.1021/jm960127s
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 香叶基香叶醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 N-(geranylgeranyloxy)phthalimide
  参考文献：
  名称：

  相对于法呢基蛋白质转移酶抑制选择性而言，香叶基香叶基二磷酸的稳定类似物具有改善的香叶基香叶基。

  摘要：

  已证明，草酰乙酰氨基（氧基）基团是香叶基香叶基蛋白质转移酶I（GGTase I）抑制剂中二磷酸部分的良好模拟物。将小烷基（Me，Et）引入二磷酸模拟部分会导致法呢基蛋白转移酶（FTase）的抑制活性进一步降低，从而相对于FTase选择性提高了GGTaseI。

  DOI：

  10.1016/j.bmcl.2003.09.035

文献信息

• Geranylgeranyl-derivatives, process for the preparation thereof and related pharmaceutical compositions
  申请人：Laboratori Baldacci SpA

  公开号：US06242433B1

  公开（公告）日：2001-06-05

  The present invention relates to novel geranylgeranyl derivatives and the pharmaceutically acceptable salts thereof having antiproliferative activity in eukaryotic cells with respect to the inhibition of protein geranygeranylation. The invention also relates to the pharmaceutical compositions containing the novel derivatives and to the process of preparation thereof.

  本发明涉及一种新型的戊二十烯基衍生物及其药学上可接受的盐，具有对真核细胞的抗增殖活性，可抑制蛋白质戊二十烷基化。本发明还涉及包含该新型衍生物的药物组合物以及其制备方法。
• NOVEL GERANYLGERANYL-DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND RELATED PHARMACEUTICAL COMPOSITIONS
  申请人：LABORATORI BALDACCI Spa

  公开号：EP0862575B1

  公开（公告）日：2004-02-11
• US6242433B1
  申请人：——

  公开号：US6242433B1

  公开（公告）日：2001-06-05
• Stable analogues of geranylgeranyl diphosphate possessing improved geranylgeranyl versus farnesyl protein transferase inhibitory selectivity
  作者：Filippo Minutolo、Simone Bertini、Laura Betti、Romano Danesi、Gianbattista Gervasi、Gino Giannaccini、Chiara Papi、Giorgio Placanica、Silvia Barontini、Simona Rapposelli、Marco Macchia

  DOI：10.1016/j.bmcl.2003.09.035

  日期：2003.12

  groups have proven to be good mimics of the diphosphate portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety caused a further decrease in collateral farnesyl protein transferase (FTase) inhibitory activity, thereby improving GGTase I over FTase selectivity.

  已证明，草酰乙酰氨基（氧基）基团是香叶基香叶基蛋白质转移酶I（GGTase I）抑制剂中二磷酸部分的良好模拟物。将小烷基（Me，Et）引入二磷酸模拟部分会导致法呢基蛋白转移酶（FTase）的抑制活性进一步降低，从而相对于FTase选择性提高了GGTaseI。
• Geranylgeranyl Diphosphate-Based Inhibitors of Post-Translational Geranylgeranylation of Cellular Proteins
  作者：Marco Macchia、Nicoletta Jannitti、Gianbattista Gervasi、Romano Danesi

  DOI：10.1021/jm960127s

  日期：1996.1.1

  A novel series of stable analogs of geranylgeranyl diphosphate (GGdP) are described in which the biologically labile diphosphate moiety of GGdP is replaced by portions that can act as stable isosters. The compounds inhibited the geranylgeranyltransferase activity in whole PC-3 prostate cancer cells, as determined by the inhibition of post-translational isoprenylation of the small GTP-binding protein p21rap 1 and the accumulation of unprocessed p21rap 1 in the cytosolic fraction. However, the compounds did not affect the farnesylation of p21ras, as shown by protein immunoprecipitation after whole cell labeling with [H-3]-(R,S)-mevalonolactone. Despite the absence of effects on post-translational processing of p21ras, these compounds proved to be cytotoxic for prostate cancer cells, with half-maximal inhibition of cell growth obtained in the range 18.5-35.1 mu M. The GGdP analogs described in the this study are novel, non-peptidic inhibitors of geranylgeranylation that may be active as antitumor agents.