tetrapivaloyloxymethyl (E)-1,1-bis(4,8-dimethyl-nona-3,7-dienyl)-1,1-bisphosphonate | 878143-04-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tetrapivaloyloxymethyl (E)-1,1-bis(4,8-dimethyl-nona-3,7-dienyl)-1,1-bisphosphonate
• 英文别名: [[(6E,11E)-9-[bis(2,2-dimethylpropanoyloxymethoxy)phosphoryl]-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraen-9-yl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• CAS: 878143-04-5
• 化学式: C₄₅H₇₈O₁₄P₂
• 分子量: 905.053
• InChiKey: PCSFTZHNYWJSHB-DKKRNIPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.9
• 重原子数：
  61
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  176
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  tetramethyl (E)-1,1-bis(4,8-dimethylnona-3,7-dienyl)-1,1-bisphosphonate 、 特戊酸氯甲酯 在 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以18%的产率得到tetrapivaloyloxymethyl (E)-1,1-bis(4,8-dimethyl-nona-3,7-dienyl)-1,1-bisphosphonate
  参考文献：
  名称：

  Geranylgeranyl pyrophosphate synthase inhibitors

  摘要：

  这项发明提供了一种新型的焦磷酸合酶抑制剂，其化学式为I，以及包含这种抑制剂的组合物和使用它们的方法。

  公开号：

  US20060052347A1

文献信息

• Pivaloyloxymethyl-modified isoprenoid bisphosphonates display enhanced inhibition of cellular geranylgeranylation
  作者：Andrew J. Wiemer、Jose S. Yu、Larry W. Shull、Rocky J. Barney、Brian M. Wasko、Kimberly M. Lamb、Raymond J. Hohl、David F. Wiemer

  DOI：10.1016/j.bmc.2008.02.016

  日期：2008.4.1

  Nitrogenous bisphosphonate inhibitors of farnesyl disphosphate synthase have been used clinically for treatment of bone disease. Because many of their effects may be mediated by depletion of geranylgeranyl diphosphate, our group has sought compounds that do this more directly through inhibition of geranylgeranyl diphosphate synthase and we have discovered a number of isoprenoid-containing bisphosphonates that selectively inhibit this enzyme. These compounds have a high negative charge at physiological pH which is necessary for inhibition of the enzyme but may limit their ability to enter cells. Therefore, chemical modifications that mask this charge may enhance their cellular potency. We now have synthesized novel pivaloyloxymethyl-modified isoprenoid bisphosphonates and investigated their ability to inhibit protein geranylgeranylation within cells. We have found that addition of pivaloyloxymethyl moieties to isoprenoid bisphosphonates increases their potency towards cellular geranylgeranylation even though this modification decreases their in vitro inhibition of geranylgeranyl diphosphate synthase. Pivaloyloxymethyl modifications more effectively increase the cellular activity of the more polar isoprenoid bisphosphonates. These results reveal structural relationships between in vitro and cellular activity which may serve as the basis for future development of more potent and/or druglike inhibitors of geranylgeranyl diphosphate synthase. (C) 2008 Elsevier Ltd. All rights reserved.
• Geranylgeranyl pyrophosphate synthase inhibitors
  申请人：Wiemer F. David

  公开号：US20060052347A1

  公开（公告）日：2006-03-09

  The invention provides novel pyrophosphate synthase inhibitors of formula I as well as compositions comprising such inhibitors and methods for their use.

  这项发明提供了一种新型的焦磷酸合酶抑制剂，其化学式为I，以及包含这种抑制剂的组合物和使用它们的方法。