tetraethyl 3-amino-propane-1,1-bisphosphonate | 141473-49-6

• 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 3-amino-propane-1,1-bisphosphonate
• 英文别名: tetraethyl 3-aminopropylidene-1,1-bisphosphonate；tetraethyl 3-aminopropyl 1,1-bis(phosphonate)；Tetraethyl(3-aminopropylidene)bisphosphonate；3,3-bis(diethoxyphosphoryl)propan-1-amine
• CAS: 141473-49-6
• 化学式: C₁₁H₂₇NO₆P₂
• mdl: MFCD02684019
• 分子量: 331.286
• InChiKey: FPOJOLJEOJMAHY-UHFFFAOYSA-N

物化性质

• 沸点：
  424.5±40.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  20
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2922499990

反应信息

• 作为反应物：
  描述：

  tetraethyl 3-amino-propane-1,1-bisphosphonate 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 (1-(Diethoxy-phosphoryl)-3-{3-[2-(3,4-dihydroxy-phenyl)-ethylcarbamoyl]-propionylamino}-propyl)-phosphonic acid diethyl ester
  参考文献：
  名称：

  A Biocompatible Method of Decorporation:  Bisphosphonate-Modified Magnetite Nanoparticles to Remove Uranyl Ions from Blood

  摘要：

  We report on the use of bisphosphonate to functionalize Fe3O4 magnetic nanoparticles via dopamine (DA) linkage. Using tetraethyl-3-aminopropane-1,1-bisphosphonate (BP) as the functional molecule, we created a system with an Fe3O4-DA-BP nanostructure, which possesses high specificity for removing uranyl ions from water or blood. This work demonstrates that magnetic nanoparticles, combined with specific receptor-ligand interactions, promise a sensitive and rapid platform for the detection, recovery, and decorporation of metal toxins from biological environment.

  DOI：

  10.1021/ja0651355
• 作为产物：
  描述：

  亚甲基二磷酸四乙酯 在 palladium 10% on activated carbon 、 水 、 氢气 、 sodium methylate 、 二乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 46.0h， 生成 tetraethyl 3-amino-propane-1,1-bisphosphonate
  参考文献：
  名称：

  二酮吡咯并吡咯双膦酸酯共轭物：用于体外骨成像的新型荧光探针

  摘要：

  据报道，通过点击化学策略以靶骨组织为靶标并监测相互作用，在不寻常的红色荧光二酮吡咯并吡咯（DPP）单元与双膦酸酯（BP）前体之间合成了共轭分子。经过深入研究，发现在γ-叠氮基而不是β-叠氮基BP与炔基官能化的DPP荧光基团之间通过三唑单元进行偶联是成功的策略。成功地证明了破骨细胞上DPP-BP偶联物的可视化和特定的抗吸收活性。

  DOI：

  10.1002/chem.201805436

文献信息

• Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors
  作者：Daniel B. Goetz、Michelle L. Varney、David F. Wiemer、Sarah A. Holstein

  DOI：10.1016/j.bmc.2020.115604

  日期：2020.8

  synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several

  香叶基香叶基二磷酸合酶 (GGDPS) 抑制剂因其对骨髓癌多发性骨髓瘤的活性而具有潜在的治疗意义。已经制备了一系列通过酰胺键连接到类异戊二烯尾部的双膦酸盐，并在基于酶和细胞的测定中测试了抑制 GGDPS 的能力。酰胺被设计为类似于基于三唑的 GGDPS 抑制剂。几种新化合物在酶和细胞测定中均显示出 GGDPS 抑制活性，其效力取决于链长和烯烃立体化学。
• Aminoalkylbis(phosphonates): Their Complexation Properties in Solution and in the Solid State
  作者：Vojtěch Kubíček、Jan Kotek、Petr Hermann、Ivan Lukeš

  DOI：10.1002/ejic.200600615

  日期：2007.1

  bis(phosphonates) containing an amino group in the α, γ or δ position of the carbon chain have been synthesised and their acid–base and complexation properties with Cu2+, Zn2+, Ca2+, Mg2+ and Na+ ions studied by potentiometry. Determination of the stability constants of the complexes with divalent metal ions is complicated by the formation of precipitates. The results of these studies show a negligible effect

  已经合成了五种在碳链的 α、γ 或 δ 位置含有氨基的孪生双（膦酸盐），并通过电位法研究了它们的酸碱和与 Cu2+、Zn2+、Ca2+、Mg2+ 和 Na+ 离子的络合特性。与二价金属离子配合物的稳定性常数的测定由于沉淀物的形成而变得复杂。这些研究的结果表明，α 位的羟基对配体的酸碱和络合性质的影响可以忽略不计。然而，α 位氨基的存在会降低碱性，从而导致双（膦酸酯）的络合能力降低。三种不同质子化度的配体的晶体结构也已确定。氨基甲基双（膦酸）三铵盐的结构表明，质子与单质子化物质中的氮原子结合。帕米膦酸盐 [Cu2(H2pam)2}·H2O]n 的 Cu2+ 复合物的结构表明存在二聚体单元，金属中心之间的距离相对较短 (2.99 A)。这些单元形成配位聚合物链。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
• Synthesis and Hydroxyapatite Binding Activity of Bisphosphonate-Statin Conjugates (SUPPLEMENTAL FILE)
  作者：Guangyu Xu、Gaolei Zuo、Shihua Zhong、Wei Zhang

  DOI：10.2174/157017809788681356

  日期：2009.7.1

  To develop a methodology for delivering anabolic agents statins to bone, a bone targeting bisphosphonate was used as a carrier of drugs. Four statin-bisphosphonate conjugates were synthesized and examined for their bone mineral affinity in vitro by hydroxyapatite absorption method. The conjugates showed high binding activity with HAP, implying the modified statins possess the potential of bone targeting property.

  为了开发一种将同化制剂他汀类药物输送到骨骼的方法，使用了一种骨骼靶向双膦酸盐作为药物载体。我们合成了四种他汀类药物-双膦酸盐共轭物，并通过羟基磷灰石吸收法在体外检测了它们的骨矿物质亲和性。这些共轭物与羟基磷灰石具有很高的结合活性，这意味着改性他汀类药物具有潜在的骨靶向特性。
• Design of a radiopharmaceutical for the palliation of painful bone metastases: rhenium-186-labeled bisphosphonate derivative
  作者：Kazuma Ogawa、Takahiro Mukai、Yasushi Arano、Hirofumi Hanaoka、Kazuyuki Hashimoto、Hiroshi Nishimura、Hideo Saji

  DOI：10.1002/jlcr.864

  日期：2004.10.15

  To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we designed a bisphosphonate derivative attached to a stable 186Re-monoaminemonoamidedithiol (MAMA) chelate (186Re-MAMA-BP) to improve the instability of 186Re-HEDP. The precursor (Tr-MAMA-BP) of 186Re-MAMA-BP was synthesized by coupling the carboxyl group of the Tr-MAMA derivative with the amino group of the bisphosphonate derivative. This 186Re-labeled compound was prepared by a ligand exchange reaction using 186Re-glucoheptonate with a radiochemical yield of 32.0 ± 4.1%. In the incubation study in buffered solution (pH 7.0), 186Re-MAMA-BP was more stable than 186Re-HEDP. This suggests that 186Re-MAMA-BP is a potential radiopharmaceutical for the palliation of painful bone metastases. Copyright © 2004 John Wiley & Sons, Ltd.

  为了根据双功能放射性药物的概念开发一种用于缓解骨转移疼痛的放射性药物，我们设计了一种附着于稳定的 186Re-monoaminemonoamidedithiol (MAMA) 螯合物（186Re-MAMA-BP）上的双磷酸盐衍生物，以改善 186Re-HEDP 的不稳定性。186Re-MAMA-BP 的前体（Tr-MAMA-BP）是通过将 Tr-MAMA 衍生物的羧基与双膦酸盐衍生物的氨基偶联而合成的。这种 186Re 标记的化合物是通过使用 186Re- Glucoheptonate 进行配体交换反应制备的，放射化学收率为 32.0 ± 4.1%。在缓冲溶液（pH 值为 7.0）中的孵育研究中，186Re-MAMA-BP 比 186Re-HEDP 更加稳定。这表明，186Re-MAMA-BP 是一种有潜力用于缓解骨转移疼痛的放射性药物。Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.
• NOVEL FLUORINE-CONTAINING BISPHOSPHONIC ACID DERIVATIVE AND USE THEREOF
  申请人：NAGASAKI UNIVERSITY

  公开号：US20180022769A1

  公开（公告）日：2018-01-25

  A series of fluorine-containing bisphosphonic acids in which an alkylamine side chain is added, a series of fluorine-containing bisphosphonic acids in which an amino group substituted by a heterocyclic group or a heterocyclic group containing a nitrogen atom is added, to the carbon atom of P—C(F)—P, and a series of fluorine-containing bisphosphonate derivatives in which the acid moiety thereof is esterified by an alkoxymethyl group such as POM group, n-butanoyloxymethyl (BuOM) group and the like, that is, the fluorine-containing bisphosphonic acid and fluorine-containing bisphosphonate derivative represented by the following formula (I): wherein each symbol is as defined in the DESCRIPTION, can efficiently induce proliferation of peripheral blood γδ T cells that express Vγ2Vδ2 T cell receptor having superior cytotoxicity against tumor cells and virus infected cells, immunize tumor cells and virus infected cells, and can induce cytotoxicity by γδ T cells.

  一系列含氟双膦酸，其中添加了烷胺侧链，一系列含氟双膦酸，其中添加了由杂环基团取代的氨基或含氮原子的杂环基团，连接到P-C(F)-P的碳原子上，以及一系列含氟双膦酸衍生物，其中其酸基部分通过POM基团、正丁酰氧甲基（BuOM）基团等烷氧甲基基团酯化，即以下式（I）所代表的含氟双膦酸和含氟双膦酸衍生物： 其中每个符号如描述中所定义，可以有效诱导表达具有对肿瘤细胞和病毒感染细胞具有优越细胞毒性的Vγ2Vδ2 T细胞受体的外周血γδ T细胞增殖，免疫肿瘤细胞和病毒感染细胞，并且可以通过γδ T细胞诱导细胞毒性。