(6E,10E,15E,19E)-2,6,10,16,20,24-hexamethyl-2,6,10,15,19,23-pentacosahexaenyl-13,13-bisphosphonic acid

• 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: (6E,10E,15E,19E)-2,6,10,16,20,24-hexamethyl-2,6,10,15,19,23-pentacosahexaenyl-13,13-bisphosphonic acid
• 英文别名: bisfarnesylmethylenebiphosphonic acid；[(6E,10E,15E,19E)-2,6,10,16,20,24-hexamethyl-13-phosphonopentacosa-2,6,10,15,19,23-hexaen-13-yl]phosphonic acid
• 化学式: C₃₁H₅₄O₆P₂
• 分子量: 584.714
• InChiKey: BMZGFAFJIOSDNA-SBEKHEBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  39
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  115
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  反,反-法呢基溴 在 2,3,5-三甲基吡啶 、 15-冠醚-5 、 三甲基溴硅烷 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (6E,10E,15E,19E)-2,6,10,16,20,24-hexamethyl-2,6,10,15,19,23-pentacosahexaenyl-13,13-bisphosphonic acid
  参考文献：
  名称：

  Synthesis and biological activity of isoprenoid bisphosphonates

  摘要：

  Bisphosphonates have been used in the clinic to treat osteoporosis and to reduce bone resorption and the accompanying pathological bone fractures that attend a number of malignancies including multiple myeloma and cancers of the prostate, breast, and lung. There is also evidence that some bisphosphonates have direct anticancer activity. Expansion of the current class of bisphosphonates may lead to compounds that more selectively and potently target these cancers through inhibition of the mevalonate pathway. To this end, a set of dialkyl bisphosphonates bearing isoprenoid chains of varying lengths has been synthesized. Some of these compounds were found to have biological activity on post-translational processing of the oncogenic small GTPases, Ras and Rapla, in human-derived K562 leukemia cells. Most importantly, these compounds impair protein geranylgeranylation and not protein farnesylation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.010

文献信息

• Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate
  作者：A.R.P.M. Valentijn、O. van den Berg、G.A. van der Marel、L.H. Cohen、J.H. van Boom

  DOI：10.1016/0040-4020(94)01083-c

  日期：1995.2

  The synthesis of four new analogues (i.e.3–6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by condensation of the resulting alcohols with diethyl phosphonomethyl triflate. The preparation of 5 and

  描述了法呢基焦磷酸酯（FPP）的四个新类似物（即3–6）的合成，它们可能是角鲨烯合酶的抑制剂。通过将法呢醛与亚磷酸二乙酯或亚硫基甲基膦酸二甲酯反应，然后将所得的醇与三氟甲磺酸膦酸二乙酯缩合，可以容易地获得化合物3和4。通过分别用法呢基溴将双（二乙基膦酰基甲基）醚或亚甲基双膦酸四乙酯烷基化来完成5和6的制备。
• US5827838A
  申请人：——

  公开号：US5827838A

  公开（公告）日：1998-10-27
• Synthesis and biological activity of isoprenoid bisphosphonates
  作者：Larry W. Shull、Andrew J. Wiemer、Raymond J. Hohl、David F. Wiemer

  DOI：10.1016/j.bmc.2006.02.010

  日期：2006.6

  Bisphosphonates have been used in the clinic to treat osteoporosis and to reduce bone resorption and the accompanying pathological bone fractures that attend a number of malignancies including multiple myeloma and cancers of the prostate, breast, and lung. There is also evidence that some bisphosphonates have direct anticancer activity. Expansion of the current class of bisphosphonates may lead to compounds that more selectively and potently target these cancers through inhibition of the mevalonate pathway. To this end, a set of dialkyl bisphosphonates bearing isoprenoid chains of varying lengths has been synthesized. Some of these compounds were found to have biological activity on post-translational processing of the oncogenic small GTPases, Ras and Rapla, in human-derived K562 leukemia cells. Most importantly, these compounds impair protein geranylgeranylation and not protein farnesylation. (c) 2006 Elsevier Ltd. All rights reserved.