tetraethyl 2,2'-(2-hydroxyethylazanediyl)bis(ethan-2,1-diyl)diphosphonate | 1332338-67-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: tetraethyl 2,2'-(2-hydroxyethylazanediyl)bis(ethan-2,1-diyl)diphosphonate
• 英文别名: tetraethyl 2,2'-(2-hydroxyethylazanediyl)bis(ethane-2,1-diyl)diphosphonate；2-[Bis(2-diethoxyphosphorylethyl)amino]ethanol
• CAS: 1332338-67-6
• 化学式: C₁₄H₃₃NO₇P₂
• 分子量: 389.366
• InChiKey: ZPYPXSUPDPDFTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  24
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  94.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetraethyl 2,2'-(2-hydroxyethylazanediyl)bis(ethan-2,1-diyl)diphosphonate 在 偶氮二甲酸二异丙酯 、 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 tetraethyl 9-[(N,N-(bis-2-phosphonoethyl))-2-aminoethyl]hypoxanthine
  参考文献：
  名称：

  Synthesis of Novel N-Branched Acyclic Nucleoside Phosphonates As Potent and Selective Inhibitors of Human, Plasmodium falciparum and Plasmodium vivax 6-Oxopurine Phosphoribosyltransferases

  摘要：

  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.

  DOI：

  10.1021/jm300662d
• 作为产物：
  描述：

  2-溴乙基膦酸二乙酯 在 lithium perchlorate 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 10.0h， 生成 tetraethyl 2,2'-(2-hydroxyethylazanediyl)bis(ethan-2,1-diyl)diphosphonate
  参考文献：
  名称：

  Synthesis and characterization of novel tetrahedral copper(I) complexes comprising tridentate PNP-aminodiphosphines and tetradentate PN(X)P-substituted aminodiphosphines (X=O, S)

  摘要：

  Two series of novel tetrahedral copper(I) complexes comprising tridentate PNP-aminodiphosphines and tetradentate PN(X) P-substituted aminodiphosphines (X = O, S) have been prepared and characterized by conventional physico-chemical techniques. The first series includes '3 + 1'-type complexes comprising an aromatic PNP-aminodiphosphine and acetonitrile or triphenylphosphine. In the second series, the central amine function of the PNP-ligand was substituted with functionalized pendant arms containing ether, hydroxyl or thioether groups to enhance the chelation ability of the ligand. Fully coordinated neutral and cationic complexes were isolated. A preliminary study investigating both the labeling of Cu-64 with the prototype PN(S)P ligand and the potential cytotoxic activity of the 'cold' [Cu(PN(S)P)][BF4] complex is reported. (C) 2012 Elsevier B. V. All rights reserved.

  DOI：

  10.1016/j.ica.2012.01.012

文献信息

• Acyclic nucleoside phosphonates with unnatural nucleobases, favipiravir and allopurinol, designed as potential inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases
  作者：Tomáš Klejch、Radek Pohl、Zlatko Janeba、Minghan Sun、Dianne T. Keough、Luke W. Guddat、Dana Hocková

  DOI：10.1016/j.tet.2018.08.014

  日期：2018.10

  Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is a key enzyme of the purine salvage pathway and its activity is crucial for the survival of certain parasites e.g. Plasmodium falciparum (Pf). Acyclic nucleoside phosphonates (ANPs) containing either guanine or hypoxanthine as the purine base are inhibitors of this enzyme. In this part of a SAR study, these two naturally-occurring nucleobases

  次黄嘌呤-鸟嘌呤-黄嘌呤磷酸（HGXPRT）是嘌呤补救途径的关键酶，其活性是对某些寄生虫生存至关重要例如。恶性疟原虫（Pf）。含有鸟嘌呤或次黄嘌呤作为嘌呤碱基的无环核苷膦酸酯（ANP）是该酶的抑制剂。在SAR研究的这一部分，这两个与无环部分连接的天然存在的碱基被别嘌呤醇或favipiravir取代。通过Mitsunobu反应制备别嘌呤醇和favipiravir ANP。法维吡韦的烷基化被优化以产生N-和O-区域异构体，但是N-区域异构体在去保护条件下不稳定。因此，只有含有Favipiravir的O-异构体的ANP和含有别嘌呤醇的ANP被评估为人类HGPRT和Pf HGXPRT的潜在抑制剂。以别嘌醇为基础的两个ANP的Pf的K i值为10μM和30μMHGXPRT，但在100–150μM的浓度下不抑制人类HGPRT活性。
• 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）。
• 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。
• [EN] 6-OXOPURINE PHOSPHORIBOSYLTRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DE 6-OXOPURINE PHOSPHORIBOSYLTRANSFÉRASE
  申请人：UNIV QUEENSLAND

  公开号：WO2013166545A3

  公开（公告）日：2015-03-05
• EP2847201B1
  申请人：——

  公开号：EP2847201B1

  公开（公告）日：2017-08-16