1-(β-D-glucopyranosyl)-5-heptynyluracil | 1392420-67-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(β-D-glucopyranosyl)-5-heptynyluracil
• 英文别名: 1-(Beta-D-Glucopyranosyl)-5-(Hept-1-Yn-1-Yl)pyrimidine-2,4(1h,3h)-Dione；5-hept-1-ynyl-1-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]pyrimidine-2,4-dione
• CAS: 1392420-67-5
• 化学式: C₁₇H₂₄N₂O₇
• 分子量: 368.387
• InChiKey: ZIAKFTYLGUACKB-XYFZXANASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(β-D-glucopyranosyl)-5-heptynyluracil 在 silver nitrate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以90%的产率得到3-(β-D-glucopyranosyl)-6-pentylfuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  The binding of C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment

  摘要：

  C5-alkynyl and allcylfurano[2,3-d]pyrimidine glucopyranonucleosides have been synthesized and studied as inhibitors of glycogen phosphorylase b (GPb). Kinetic experiments have shown that most of these compounds were low micromolar inhibitors of the enzyme. The best inhibitor was 1-(beta-D-glucopyranosyl)-5-ethynyluracil (K-i = 4.7 mu M). Crystallographic analysis of these compounds in complex with GPb revealed that inhibitors with a long C5-alkynyl group exploited interactions with beta-pocket of the active site and induced significant conformational changes of the 280s loop compared to GPb in complex with compounds with a short C5-alkynyl group. The results highlight the importance in the length of the aliphatic groups used to enhance inhibitory potency for the exploitation of the hydrophobic beta-pocket. The best of the inhibitors had also a moderate effect on glycogenolysis in the cellular lever with an IC50 value of 291.4 mu M. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.029
• 作为产物：
  描述：

  1,2,3,4,6-alpha-D-葡萄糖五乙酸酯 在 copper(l) iodide 、 四(三苯基膦)钯 、 三氟甲磺酸三甲基硅酯 、 氨 、 三乙胺 、 六甲基二硅氮烷 、 糖精 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.1h， 生成 1-(β-D-glucopyranosyl)-5-heptynyluracil
  参考文献：
  名称：

  Rapid microwave-enhanced synthesis of C5-alkynyl pyranonucleosides as novel cytotoxic antitumor agents

  摘要：

  A microwave-assisted, one-pot, coupling reaction for the synthesis of C5-alkynyl-uracil and cytosine glucopyranonucleosides has been developed. The reaction is carried out under standard Sonogashira coupling conditions from glucopyranonucleosides of 5-iodouracil or 5-iodocytosine and various terminal alkynes. All compounds were evaluated for their cytostatic and antiviral activity. The 5-phenylethynyluracil pyranonucleoside derivative 6a showed the most promising cytostatic activity (50% inhibitory concentration in the lower micromolar range). No meaningful antiviral activity was recorded. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.092

文献信息

• Rapid microwave-enhanced synthesis of C5-alkynyl pyranonucleosides as novel cytotoxic antitumor agents
  作者：Athina Dimopoulou、Stella Manta、Christos Kiritsis、Dimitra-Niki Gkaragkouni、Ioannis Papasotiriou、Jan Balzarini、Dimitri Komiotis

  DOI：10.1016/j.bmcl.2012.12.092

  日期：2013.3

  A microwave-assisted, one-pot, coupling reaction for the synthesis of C5-alkynyl-uracil and cytosine glucopyranonucleosides has been developed. The reaction is carried out under standard Sonogashira coupling conditions from glucopyranonucleosides of 5-iodouracil or 5-iodocytosine and various terminal alkynes. All compounds were evaluated for their cytostatic and antiviral activity. The 5-phenylethynyluracil pyranonucleoside derivative 6a showed the most promising cytostatic activity (50% inhibitory concentration in the lower micromolar range). No meaningful antiviral activity was recorded. (C) 2013 Elsevier Ltd. All rights reserved.
• The binding of C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment
  作者：A.L. Kantsadi、S. Manta、A.-M.G. Psarra、A. Dimopoulou、C. Kiritsis、V. Parmenopoulou、V.T. Skamnaki、P. Zoumpoulakis、S.E. Zographos、D.D. Leonidas、D. Komiotis

  DOI：10.1016/j.ejmech.2012.06.029

  日期：2012.8

  C5-alkynyl and allcylfurano[2,3-d]pyrimidine glucopyranonucleosides have been synthesized and studied as inhibitors of glycogen phosphorylase b (GPb). Kinetic experiments have shown that most of these compounds were low micromolar inhibitors of the enzyme. The best inhibitor was 1-(beta-D-glucopyranosyl)-5-ethynyluracil (K-i = 4.7 mu M). Crystallographic analysis of these compounds in complex with GPb revealed that inhibitors with a long C5-alkynyl group exploited interactions with beta-pocket of the active site and induced significant conformational changes of the 280s loop compared to GPb in complex with compounds with a short C5-alkynyl group. The results highlight the importance in the length of the aliphatic groups used to enhance inhibitory potency for the exploitation of the hydrophobic beta-pocket. The best of the inhibitors had also a moderate effect on glycogenolysis in the cellular lever with an IC50 value of 291.4 mu M. (C) 2012 Elsevier Masson SAS. All rights reserved.