dimethyl (E,E,E)-[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)ethoxyphosphoryl]methylphosphonate | 191801-11-3

• 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: dimethyl (E,E,E)-[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)ethoxyphosphoryl]methylphosphonate
• 英文别名: dimethyl (E,E,E)-[[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)ethoxyphosphoryl]methyl]phosphonate；(2E,6E,10E)-1-[[dimethoxyphosphorylmethyl(ethoxy)phosphoryl]methoxy]-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraene
• CAS: 191801-11-3
• 化学式: C₂₆H₄₈O₆P₂
• 分子量: 518.611
• InChiKey: PNSAPURTTDUXFK-QGBZOTKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  34
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl (E,E,E)-[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)ethoxyphosphoryl]methylphosphonate 在 2,4,6-三甲基吡啶 、 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (E,E,E)-[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)hydroxyphosphoryl]methylphosphonic acid
  参考文献：
  名称：

  Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors

  摘要：

  The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.

  DOI：

  10.1016/j.farmac.2004.08.002
• 作为产物：
  描述：

  香叶基香叶醇 在 氢氧化钾 、 正丁基锂 、 三甲基硅烷基二乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 异丙醇 为溶剂， 反应 57.0h， 生成 dimethyl (E,E,E)-[(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyloxymethyl)ethoxyphosphoryl]methylphosphonate
  参考文献：
  名称：

  Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors

  摘要：

  The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.

  DOI：

  10.1016/j.farmac.2004.08.002

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
• Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors
  作者：Filippo Minutolo、Michela Antonello、Silvia Barontini、Simone Bertini、Laura Betti、Romano Danesi、Gianbattista Gervasi、Gino Giannaccini、Chiara Papi、Giorgio Placanica、Simona Rapposelli、Marco Macchia

  DOI：10.1016/j.farmac.2004.08.002

  日期：2004.11

  The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.