tetraethyl ((4-hydroxyphenyl)methylene)bis(phosphonate) | 188752-80-9

• 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: tetraethyl ((4-hydroxyphenyl)methylene)bis(phosphonate)
• 英文别名: tetraethyl 4-hydroxyphenylmethylene-1,1-bisphosphonate；tetraethyl-4-hydroxypenylmethylene-1,1-bisphosphonate；tetraethyl (4-hydroxyphenyl)methylene bisphosphonate；4-[Bis(diethoxyphosphoryl)methyl]phenol
• CAS: 188752-80-9
• 化学式: C₁₅H₂₆O₇P₂
• 分子量: 380.315
• InChiKey: JCERWRSGUROEIE-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C(Solv: hexane (110-54-3))
• 沸点：
  504.9±50.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tetraethyl ((4-hydroxyphenyl)methylene)bis(phosphonate) 在 三甲基溴硅烷 、 甲醇 作用下， 以 氯仿 为溶剂， 反应 32.0h， 以98%的产率得到4-Hydroxy-phenylmethan-bisphosphonsaeure
  参考文献：
  名称：

  Calix[4]arene methylenebisphosphonic acids as calf intestine alkaline phosphatase inhibitors

  摘要：

  通过在母体钙[4]烯醛中加入亚磷酸二乙酯，制备出含有一个或两个亚甲基二膦酸片段的钙[4]烯醛。与单纯的亚甲基二膦酸或 4-羟基苯基亚甲基二膦酸相比，所制备的化合物对小牛肠道碱性磷酸酶的抑制作用更强。这些磷酸化钙[4]烯的作用与部分混合型抑制作用一致。在 pH 值为 9 的 Tris-HCl 缓冲液中，钙[4]炔双亚甲基二膦酸的抑制常数 Ki 和 Ki′分别为 0.38 µM 和 2.8 µM。用二乙基膦酸盐取代大环上的磷酸分子会导致其抑制作用急剧下降。因此，利用钙杂蒽平台预组织膦酸片段为设计高效的碱性磷酸酶抑制剂提供了一种前景广阔的方法。

  DOI：

  10.1039/b409526j
• 作为产物：
  描述：

  tetraethyl-4-aminophenylmethylene-1,1-bisphosphonate 在 盐酸 、 sodium nitrite 、 水 作用下， 以 水 为溶剂， 反应 2.0h， 以50%的产率得到tetraethyl ((4-hydroxyphenyl)methylene)bis(phosphonate)
  参考文献：
  名称：

  Preparation Of Tetraethyl-4-Hydroxyphenylmethylene-1,1-Bisphosphonate By Hydroxy-De-Diazoniation of The Corresponding Diazonium Salt Of Tetraethyl-4-Aminophenylmethylene-1,1-Bisphosphonate

  摘要：

  Bisphosphonates are widely used in diagnosis and therapy of different bone diseases. They are useful agents in osteotic vectorization of antitumor and antiinflammatory drugs because of their potential to accumulate in the inorganic bone matrix hydroxylapatite. Hence, there is great interest in alkyl-bisphosphonates. containing functional groups advantageous For further synthetic modification, as structural units for coupling with the drug. We report on the synthesis of tetraethyl-4-hydroxyphenylmethylene-1,1-bisphosphonate 8 by hydroxy-de-diazoniation of the diazonium salt 7, prepared by diazotation of the corresponding amine tetraethyl-3-aminophenyl methylene-1,1-bisphosphonate 6.

  DOI：

  10.1080/10426500008076326

文献信息

• Phosphonated Fluoroquinolones, Antibacterial Analogs Thereof, and Methods for the Prevention and Treatment of Bone and Joint Infections
  申请人：Delorme Daniel

  公开号：US20080287396A1

  公开（公告）日：2008-11-20

  The present invention relates to phosphonated fluoroquinolones, antibacterial analogs thereof, and methods of using such compounds. These compounds are useful as antibiotics for prevention and/or the treatment of bone and joint infections, especially for the prevention and/or treatment of osteomyelitis.

  本发明涉及磷酸化氟喹诺酮及其抗菌类似物，以及使用这些化合物的方法。这些化合物可用作抗生素，用于预防和/或治疗骨骼和关节感染，特别是用于预防和/或治疗骨髓炎。
• Bisphosphonate Inhibitors of Mammalian Glycolytic Aldolase
  作者：Paul W. Heron、Marta Abellán-Flos、Laurent Salmon、Jurgen Sygusch

  DOI：10.1021/acs.jmedchem.8b01000

  日期：2018.12.13

  structure of mammalian aldolase in complex with naphthalene 2,6-bisphosphate (1) that served as a template for the design of bisphosphonate-based inhibitors, namely, 2-phosphate-naphthalene 6-bisphosphonate (2), 2-naphthol 6-bisphosphonate (3), and 1-phosphate-benzene 4-bisphosphonate (4). All inhibitors targeted the active site, and the most promising lead, 2, exhibited slow-binding inhibition with an overall

  糖酵解酶醛缩酶是诸如癌症和原生动物感染之类的疾病中的新兴药物靶标，所述疾病依赖于高糖酵解表型来合成腺苷5'-三磷酸和用于生物质生产的代谢前体。迄今为止，缺乏与磷酸盐衍生的抑制剂复合的酶的结构信息。因此，我们确定了哺乳动物醛缩酶与2，6-萘二甲酸萘（1）配合使用的晶体结构，该萘设计了基于双膦酸盐的抑制剂，即2-磷酸萘6-双膦酸盐（2）， 2-萘酚6-双膦酸酯（3）和1-磷酸-苯4-双膦酸酯（4）。所有抑制剂均靶向活性位点，最有前途的铅2表现出缓慢结合抑制作用，总抑制常数约为38 nM。化合物2抑制HeLa癌细胞的增殖，而表达正常表型的HEK293细胞不受抑制。晶体结构描绘了高亲和力的磷酸盐衍生抑制剂的基本特征，并为开发具有预防潜力的抑制剂提供了模板。
• 1,1-and 1,2-Bisphosphonates as apoliprotein e modulators
  申请人：Montes Flores Imber

  公开号：US20060205692A1

  公开（公告）日：2006-09-14

  The present invention relates to methods of use 1,1- and 1,2-bisphosphonate compounds to modulate apolipoprotein E levels and use of such compounds in therapy, including cardiovascular and neurological disease states.

  本发明涉及使用1,1-和1,2-双膦酸盐化合物来调节载脂蛋白E水平的方法，以及在治疗心血管和神经系统疾病状态等方面使用这些化合物的方法。
• Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis
  作者：Kelly S.E. Tanaka、Tom J. Houghton、Ting Kang、Evelyne Dietrich、Daniel Delorme、Sandra S. Ferreira、Laurence Caron、Frederic Viens、Francis F. Arhin、Ingrid Sarmiento、Dario Lehoux、Ibtihal Fadhil、Karine Laquerre、Jing Liu、Valérie Ostiguy、Hugo Poirier、Gregory Moeck、Thomas R. Parr、Adel Rafai Far

  DOI：10.1016/j.bmc.2008.09.010

  日期：2008.10

  Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering antibacterial agents to the bone may overcome the difficulties in treating this illness by effectively concentrating the antibiotic at the site of infection and by limiting the toxicity that may result from systemic exposure to the large doses conventionally used. Using bisphosphonates as osteophilic functional groups, different forms of fluoroquinolone esters were synthesized and evaluated for their ability to bind bone and to release the parent antibacterial agent. Bisphosphonated glycolamide fluoroquinolone esters were found to present a profile consistent with effective and rapid bone binding and efficient release of the active drug moiety. They were assessed for their ability to prevent bone infection in vivo and were found to be effective when the free fluoroquinolones were not (C) 2008 Elsevier Ltd. All rights reserved.
• EP1506208A4
  申请人：——

  公开号：EP1506208A4

  公开（公告）日：2006-05-24