diethyl 2-(2-hydroxyethylamino)ethylphosphonate | 942596-86-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl 2-(2-hydroxyethylamino)ethylphosphonate
• 英文别名: 2-(2-diethoxyphosphorylethylamino)ethanol
• CAS: 942596-86-3
• 化学式: C₈H₂₀NO₄P
• 分子量: 225.225
• InChiKey: ZZAYHRJTSHISLG-UHFFFAOYSA-N

物化性质

• 沸点：
  353.4±22.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  14
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 2-(2-hydroxyethylamino)ethylphosphonate 在 偶氮二甲酸二异丙酯 、 水 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 48.0h， 生成 9-[(N-(3-methoxy-3-oxopropyl)-N-(2-diethoxyphosphorylethyl))-2-aminoethyl]hypoxanthine
  参考文献：
  名称：

  [EN] 6-OXOPURINE PHOSPHORIBOSYLTRANSFERASE INHIBITORS
  [FR] INHIBITEURS DE 6-OXOPURINE PHOSPHORIBOSYLTRANSFÉRASE

  摘要：

  公开号：

  WO2013166545A3
• 作为产物：
  描述：

  2-溴乙基膦酸二乙酯 在 1,3-双[3,5-双(三氟甲基)苯基]硫脲 、 三乙胺 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 23.0h， 生成 diethyl 2-(2-hydroxyethylamino)ethylphosphonate
  参考文献：
  名称：

  硫脲催化的胺与膦酸乙烯酯和次膦酸酯的共轭加成

  摘要：

  硫脲催化剂活化 α,β-不饱和膦酸盐和次膦酸盐，通过胺进行共轭加成，得到 β-氨基膦酸盐和 β-氨基次膦酸盐。有机催化方法用于合成 15 β-氨基膦酸盐和 - 亚膦酸盐，产率高达 99%。一个克级的例子以 99% 的分离产率和 97% 的催化剂回收率提供了相应的 β-氨基膦酸酯。基于机械实验，磷酰氧和硫脲之间的氢键被认为在底物活化中起着至关重要的作用。

  DOI：

  10.1039/d2ob02116a

文献信息

• 6-OXOPURINE PHOSPHORIBOSYLTRANSFERASE INHIBITORS
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：US20150099722A1

  公开（公告）日：2015-04-09

  The invention relates to compounds which are useful as inhibitors of 6-oxopurine phosphoribosyltransferases such as hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT).

  本发明涉及一种化合物，该化合物可用作6-氧嘌呤磷酸核糖转移酶的抑制剂，例如次黄嘌呤鸟嘌呤-(黄嘌呤)磷酸核糖转移酶（HG（X）PRT）。
• 6-oxopurine phosphoribosyltransferase inhibitors
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：US09200020B2

  公开（公告）日：2015-12-01

  The invention relates to compounds which are useful as inhibitors of 6-oxopurine phosphoribosyltransferases such as hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT).

  本发明涉及一种化合物，其可用作6-氧嘌呤磷酸核糖转移酶抑制剂，例如次黄嘌呤鸟嘌呤-（黄嘌呤）磷酸核糖转移酶（HG（X）PRT）的抑制剂。
• Synthesis and anti-trypanosomal evaluation of novel N-branched acyclic nucleoside phosphonates bearing 7-aryl-7-deazapurine nucleobase
  作者：Karolína Vaňková、Eva Doleželová、Eva Tloušťová、Dana Hocková、Alena Zíková、Zlatko Janeba

  DOI：10.1016/j.ejmech.2022.114559

  日期：2022.9

  A series of novel 7-aryl-7-deazaadenine-based N-branched acyclic nucleoside phosphonates (aza-ANPs) has been prepared using the optimized Suzuki cross-coupling reaction as the key synthetic step. The final free phosphonates 15a-h were inactive, due to their inefficient transport across cell membranes, but they inhibited Trypanosoma brucei adenine phosphoribosyltransferase (TbrAPRT1) with Ki values

  以优化的 Suzuki 交叉偶联反应为关键合成步骤，制备了一系列新型 7-aryl-7-deazaadenine 基N支链无环核苷膦酸酯 (aza-ANPs)。最终的游离膦酸盐15a-h没有活性，因为它们在细胞膜上的转运效率低下，但它们抑制了布氏锥虫腺嘌呤磷酸核糖基转移酶 ( Tbr APRT1)，K i值为 1.7–14.1 μM。相应的膦酰二酰胺前药14a-h在具有 EC 50的基于布氏锥虫细胞的测定中表现出抗锥虫活性值在 0.58–6.8 μM 范围内。7-(4-Methoxy)phenyl-7-deazapurine 衍生物14h含有两个膦酸盐部分，是该系列中最有效的抗锥虫药物，EC 50  = 0.58 μM 和 SI = 16。最后，膦酰二胺前药14a-h对测试的白血病和/或癌细胞系表现出低微摩尔细胞毒性。
• Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases
  作者：Dana Hocková、Zlatko Janeba、Lieve Naesens、Michael D. Edstein、Marina Chavchich、Dianne T. Keough、Luke W. Guddat

  DOI：10.1016/j.bmc.2015.07.038

  日期：2015.9

  Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases (PRTs), key enzymes of the purine salvage pathway. Chemical modifications, based on the crystal structures of several inhibitors in complex with the human PRTase, led to the design of a new class of inhibitors-the aza-ANPs. Because of the negative charges of the phosphonic acid moiety, their ability to cross cell membranes is, however, limited. Thus, phosphoramidate prodrugs of the aza-ANPs were prepared to improve permeability. These prodrugs arrest parasitemia with IC50 values in the micromolar range against Plasmodium falciparum-infected erythrocyte cultures (both chloroquine-sensitive and chloroquine-resistant Pf strains). The prodrugs exhibit low cytotoxicity in several human cell lines. Thus, they fulfill two essential criteria to qualify them as promising antimalarial drug leads. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis of Novel <i>N</i>-Branched Acyclic Nucleoside Phosphonates As Potent and Selective Inhibitors of Human, Plasmodium falciparum and Plasmodium vivax 6-Oxopurine Phosphoribosyltransferases
  作者：Dana Hocková、Dianne T. Keough、Zlatko Janeba、Tzu-Hsuan Wang、John de Jersey、Luke W. Guddat

  DOI：10.1021/jm300662d

  日期：2012.7.12

  Hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT) is crucial for the survival of malarial parasites Plasmodium falciparum (Pf) and Plasmodium vivax (Pv). Acyclic nucleoside phosphonates (ANPs) are inhibitors of HG(X)PRT and arrest the growth of Pf in cell culture. Here, a novel class of ANPs containing trisubstituted nitrogen (aza-ANPs) has been synthesized. These compounds have a wide range of K-i values and selectivity for human HGPRT, PfHGXPRT, and PvHGPRT. The most selective and potent inhibitor of PfHGXPRT is 9-N-(3-methoxy-3-oxopropyl)-N-(2-phosphonoethyl)-2-aminoethyl]hypoxanthine (K-i = 100 nM): no inhibition could be detected against the human enzyme. This compound exhibits the highest ever reported selectivity for PfHGXPRT compared to human HGPRT. For PvHGPRT, 9-[N-(2-carboxyethyl)-N-(2-phosphonoethyl)-2-aminoethyl]guanine has a Ki of SO nM, the best inhibitor discovered for this enzyme to date. Docking of these compounds into the known structures of human HGPRT in complex with ANP-based inhibitors suggests reasons for the variations in affinity, providing insights for the design of antimalarial drug candidates.