9-[(N-(3-cyanopropyl)-N-(2-diethoxyphosphorylethyl))-2-aminoethyl]hypoxanthine | 1383381-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-[(N-(3-cyanopropyl)-N-(2-diethoxyphosphorylethyl))-2-aminoethyl]hypoxanthine
• 英文别名: diethyl 9-[(N-(2-cyanopropyl)-N-(2-phosphonoethyl))-2-aminoethyl]hypoxanthine；4-[2-diethoxyphosphorylethyl-[2-(6-oxo-1H-purin-9-yl)ethyl]amino]butanenitrile
• CAS: 1383381-87-0
• 化学式: C₁₇H₂₇N₆O₄P
• 分子量: 410.413
• InChiKey: CXWHWWOHRZHUPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-[(N-(3-cyanopropyl)-N-(2-diethoxyphosphorylethyl))-2-aminoethyl]hypoxanthine 在 吡啶 、 2,2'-二硫二吡啶 、 三乙胺 、 三苯基膦 作用下， 反应 48.0h， 生成 (2S,2'S)-diethyl-2,2'-{[2-((3-cyanopropyl)(2-(guanin-9-yl)ethyl)amino)ethyl]phosphoryl}bis(azanediyl)bis(3-phenylpropanoate)
  参考文献：
  名称：

  Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2015.07.038
• 作为产物：
  描述：

  diethyl 2-((3-cyanopropyl)(2-hydroxyethyl)amino)ethylphosphonate 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 9-[(N-(3-cyanopropyl)-N-(2-diethoxyphosphorylethyl))-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

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）。
• [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
• US9200020B2
  申请人：——

  公开号：US9200020B2

  公开（公告）日：2015-12-01