tetraethyl (Z)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate | 153751-16-7

• 英文名称: tetraethyl (Z)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
• CAS: 153751-16-7
• 化学式: C₁₉H₃₈O₆P₂
• 分子量: 424.455
• InChiKey: OTZSFUJWPCBJRM-SDXDJHTJSA-N

物化性质

• 沸点：
  509.0±50.0 °C(predicted)
• 密度：
  1.052±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.93
• 重原子数：
  27.0
• 可旋转键数：
  15.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tetraethyl (Z)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate 在 2,4,6-三甲基吡啶 、 三甲基溴硅烷 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以45%的产率得到tetrasodium (Z)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
  参考文献：
  名称：

  Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors

  摘要：

  Nitrogenous bisphosphonates are used clinically to reduce bone resorption associated with osteoporosis or metastatic bone disease, and are recognized as inhibitors of farnesyl diphosphate synthase. Inhibition of this enzyme decreases cellular levels of both farnesyl diphosphate and geranylgeranyl diphosphate which results in a variety of downstream biological effects including inhibition of protein geranylgeranylation. Our lab recently has prepared several isoprenoid bisphosphonates that inhibit protein geranylgeranylation and showed that one selectively inhibits geranylgeranyl diphosphate synthase. This results in depletion of intracellular geranylgeranyl diphosphate and impacts protein geranylgeranylation but does not affect protein farnesylation. To clarify the structural features of isoprenoid bisphosphonates that account for their geranylgeranyl diphosphate synthase inhibition, we have prepared a new group of isoprenoid bisphosphonates. The complete set of compounds has been tested for in vitro inhibition of human recombinant geranylgeranyl diphosphate synthase and cellular inhibition of protein geranylgeranylation. These results show some surprising relationships between in vitro and cellular activity, and will guide development of clinical agents directed at geranylgeranyl diphosphate synthase. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.029
• 作为产物：
  描述：

  亚甲基二磷酸四乙酯 、 (Z)-neryl bromide 在 15-冠醚-5 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以29%的产率得到tetraethyl (Z)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
  参考文献：
  名称：

  Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors

  摘要：

  Nitrogenous bisphosphonates are used clinically to reduce bone resorption associated with osteoporosis or metastatic bone disease, and are recognized as inhibitors of farnesyl diphosphate synthase. Inhibition of this enzyme decreases cellular levels of both farnesyl diphosphate and geranylgeranyl diphosphate which results in a variety of downstream biological effects including inhibition of protein geranylgeranylation. Our lab recently has prepared several isoprenoid bisphosphonates that inhibit protein geranylgeranylation and showed that one selectively inhibits geranylgeranyl diphosphate synthase. This results in depletion of intracellular geranylgeranyl diphosphate and impacts protein geranylgeranylation but does not affect protein farnesylation. To clarify the structural features of isoprenoid bisphosphonates that account for their geranylgeranyl diphosphate synthase inhibition, we have prepared a new group of isoprenoid bisphosphonates. The complete set of compounds has been tested for in vitro inhibition of human recombinant geranylgeranyl diphosphate synthase and cellular inhibition of protein geranylgeranylation. These results show some surprising relationships between in vitro and cellular activity, and will guide development of clinical agents directed at geranylgeranyl diphosphate synthase. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.029