2-(N-dodecyl,N-methylamino)ethylidene-1,1-bisphosphonic acid | 1059677-25-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 2-(N-dodecyl,N-methylamino)ethylidene-1,1-bisphosphonic acid
• 英文别名: {2-[Dodecyl(methyl)amino]-1-phosphonoethyl}phosphonic acid；[2-[dodecyl(methyl)amino]-1-phosphonoethyl]phosphonic acid
• CAS: 1059677-25-6
• 化学式: C₁₅H₃₅NO₆P₂
• 分子量: 387.394
• InChiKey: FQYMJTHEUPKDPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tetraethyl (2-(dodecyl(methyl)amino)ethane-1,1-diyl)bis(phosphonate) 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 生成 2-(N-dodecyl,N-methylamino)ethylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Inhibition of Geranylgeranyl Diphosphate Synthase by Bisphosphonates: A Crystallographic and Computational Investigation

  摘要：

  We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg2+ that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 angstrom. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents.

  DOI：

  10.1021/jm800325y

文献信息

• Inhibition of Geranylgeranyl Diphosphate Synthase by Bisphosphonates: A Crystallographic and Computational Investigation
  作者：Michael P. Hudock、Yonghui Zhang、Rey-Ting Guo、Rong Cao、Joo Hwan No、Po-Huang Liang、Tzu-Ping Ko、Tao-Hsin Chang、Shiou-chi Chang、Yongcheng Song、Jordan Axelson、Anup Kumar、Andrew H.-J. Wang、Eric Oldfield

  DOI：10.1021/jm800325y

  日期：2008.9.25

  We report the X-ray structures of several bisphosphonate inhibitors of geranylgeranyl diphosphate synthase, a target for anticancer drugs. Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg2+ that occupy the same position as found in FPP synthase. However, each of three "V-shaped" bisphosphonates bind to both the FPP and GGPP sites. Using the Glide program, we reproduced the binding modes of 10 bisphosphonates with an rms error of 1.3 angstrom. Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. These results show that some GGPPS inhibitors can occupy both substrate and product site and that binding modes as well as activity can be accurately predicted, facilitating the further development of GGPPS inhibitors as anticancer agents.