diethyl [(3R)-3-[({2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-hydroxybutyl]phosphonate | 1404216-95-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: diethyl [(3R)-3-[({2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-hydroxybutyl]phosphonate
• 英文别名: 2-chloro-7-[[[(2R)-4-diethoxyphosphoryl-1-hydroxybutan-2-yl]amino]methyl]-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one
• CAS: 1404216-95-0
• 化学式: C₁₅H₂₄ClN₄O₅P
• 分子量: 406.806
• InChiKey: VDXYODJXSIGBIC-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl [(3R)-3-[({2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-hydroxybutyl]phosphonate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 以96%的产率得到diethyl [(3R)-4-hydroxy-3-[({4-hydroxy-5Hpyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]butyl]phosphonate hydrochloride
  参考文献：
  名称：

  Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

  摘要：

  The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.016
• 作为产物：
  描述：

  4-(tert-butoxy)-2-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde 在 盐酸 、 2-甲基吡啶-N-甲硼烷 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.17h， 生成 diethyl [(3R)-3-[({2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl}methyl)amino]-4-hydroxybutyl]phosphonate
  参考文献：
  名称：

  Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

  摘要：

  The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.016

文献信息

• [EN] PHOSPHORIBOSYLTRANSFERASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE PHOSPHORIBOSYLTRANSFÉRASES ET LEURS UTILISATIONS
  申请人：IND RES LTD

  公开号：WO2012150866A1

  公开（公告）日：2012-11-08

  The invention relates to compounds of formula (I) that are inhibitors of hypoxanthine and/or guanine purine phosphoribosyltransferases and to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and methods of treating diseases or conditions in which it is desirable to inhibit hypoxanthine and/or guanine purine phosphoribosyltransferases. Such diseases include malaria.

  这项发明涉及到式（I）的化合物，这些化合物是次黄嘌呤和/或鸟嘌呤磷酸核糖转移酶的抑制剂，以及含有这些化合物的药物组合物、制备这些化合物的方法，以及治疗希望抑制次黄嘌呤和/或鸟嘌呤磷酸核糖转移酶的疾病或症状的方法。这些疾病包括疟疾。
• Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
  作者：Keith Clinch、Douglas R. Crump、Gary B. Evans、Keith Z. Hazleton、Jennifer M. Mason、Vern L. Schramm、Peter C. Tyler

  DOI：10.1016/j.bmc.2013.02.016

  日期：2013.9

  The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. (C) 2013 Elsevier Ltd. All rights reserved.