[(3Z)-4,8-dimethyl-1-phosphononona-3,7-dienyl]phosphonic acid | 1008852-07-0

• 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: [(3Z)-4,8-dimethyl-1-phosphononona-3,7-dienyl]phosphonic acid
• CAS: 1008852-07-0
• 化学式: C₁₁H₂₂O₆P₂
• 分子量: 312.24
• InChiKey: HMRLDZHPNDPQNS-YFHOEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  115
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  特戊酸氯甲酯 、 [(3Z)-4,8-dimethyl-1-phosphononona-3,7-dienyl]phosphonic acid 在 sodium iodide 作用下， 以29%的产率得到[[(3Z)-1-[bis(2,2-dimethylpropanoyloxymethoxy)phosphoryl]-4,8-dimethylnona-3,7-dienyl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
  参考文献：
  名称：

  Pivaloyloxymethyl-modified isoprenoid bisphosphonates display enhanced inhibition of cellular geranylgeranylation

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.02.016

文献信息

• Squalene synthetase inhibitory composition and use thereof
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0541037A2

  公开（公告）日：1993-05-12

  There is provided a squalene inhibitory composition containing 1,1-bisphosphonic acid compound, a lower alkyl ester thereof or a salt thereof, which is useful as a treating agent for hypercholesterolemia. There are also provided novel compounds having squalene synthetase inhibitory activity and a pharmaceutical composition for treating hypercholesterolemia containing a 1,1-bisphosphonic compound, a lower alkyl ester thereof or a salt thereof.

  提供了一种角鲨烯抑制剂组合物，其中含有 1，1-二膦酸化合物、其低级烷基酯或其盐，可用作高胆固醇血症的治疗剂。还提供了具有角鲨烯合成酶抑制活性的新型化合物，以及一种治疗高胆固醇血症的药物组合物，该组合物含有1,1-二膦酸化合物、其低级烷基酯或其盐。
• US5624917A
  申请人：——

  公开号：US5624917A

  公开（公告）日：1997-04-29