(2Z,6E)-3-(3-methyl-1-but-2-enyl)-7,11-dimethyldodeca-2,6,10-trien-1-yl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate

• 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: (2Z,6E)-3-(3-methyl-1-but-2-enyl)-7,11-dimethyldodeca-2,6,10-trien-1-yl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate
• 英文别名: (2Z,6E,10)-3-(3-methyl-1-but-2-enyl)-7,11-dimethyldodeca-2,6,10-trien-1-yl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyi)phosphoramidate；(2Z,10E)-3-(Methylbut-2-enyl)-7,11,15-trimethylhexadeca-2,6,10,14-tetraen-1-yl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl) phosphoramidate；4-chloro-N-[[(2Z,6E)-7,11-dimethyl-3-(3-methylbut-2-enyl)dodeca-2,6,10-trienoxy]-[(5-nitrofuran-2-yl)methoxy]phosphoryl]-N-methylbutan-1-amine
• 化学式: C₂₉H₄₆ClN₂O₆P
• 分子量: 585.121
• InChiKey: AWDAFDZLUZUOKI-GGGHJSHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  39
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  97.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2Z,6E)-3-(3-methylbut-2-enyl)-7,11-dimethyldodeca-2,6,10-trien-1-ol 、 5-硝基糠醇 、 4-氯-N-甲基丁-1-胺盐酸盐 以62%的产率得到(2Z,6E)-3-(3-methyl-1-but-2-enyl)-7,11-dimethyldodeca-2,6,10-trien-1-yl 5-nitrofurfuryl N-methyl-N-(4-chlorobutyl)phosphoramidate
  参考文献：
  名称：

  Synthesis, Biochemical, and Cellular Evaluation of Farnesyl Monophosphate Prodrugs as Farnesyltransferase Inhibitors

  摘要：

  Certain farnesyl diphosphate (FPP) analogs are potent inhibitors of the potential anticancer drug target protein farnesyltransferase (FTase), but these compounds are not suitable as drug candidates. Thus, phosphoramidate prodrug derivatives of the monophosphate precursors of FPP-based FTase inhibitors have been synthesized. The monophosphates themselves were significantly more potent inhibitors of FTase than the corresponding FPP analogs. The effects of the prodrug 5b (a derivative of 3-allylfarnesyl monophosphate) have been evaluated on prenylation of RhoB and on the cell cycle in a human malignant schwannoma cell line (STS-26T). In combination treatments, 1-3 mu M 5b plus 1 mu M lovastatin induced a significant inhibition of RhoB prenylation, and a combination of these drugs at 1 mu M each also resulted in significant cell cycle arrest in G(1). Indeed, combinations as low as 50 nM lovastatin + 1 mu M 5c or 250 nM lovastatin + 50 nM 5c were highly cytostatic in STS-26T cell culture.

  DOI：

  10.1021/jm0701829

文献信息

• Synthesis, Biochemical, and Cellular Evaluation of Farnesyl Monophosphate Prodrugs as Farnesyltransferase Inhibitors
  作者：Michelle K. Clark、Sarah A. Scott、Jonathan Wojtkowiak、Rosemarie Chirco、Patricia Mathieu、John J. Reiners,、Raymond R. Mattingly、Richard F. Borch、Richard A. Gibbs

  DOI：10.1021/jm0701829

  日期：2007.7.1

  Certain farnesyl diphosphate (FPP) analogs are potent inhibitors of the potential anticancer drug target protein farnesyltransferase (FTase), but these compounds are not suitable as drug candidates. Thus, phosphoramidate prodrug derivatives of the monophosphate precursors of FPP-based FTase inhibitors have been synthesized. The monophosphates themselves were significantly more potent inhibitors of FTase than the corresponding FPP analogs. The effects of the prodrug 5b (a derivative of 3-allylfarnesyl monophosphate) have been evaluated on prenylation of RhoB and on the cell cycle in a human malignant schwannoma cell line (STS-26T). In combination treatments, 1-3 mu M 5b plus 1 mu M lovastatin induced a significant inhibition of RhoB prenylation, and a combination of these drugs at 1 mu M each also resulted in significant cell cycle arrest in G(1). Indeed, combinations as low as 50 nM lovastatin + 1 mu M 5c or 250 nM lovastatin + 50 nM 5c were highly cytostatic in STS-26T cell culture.