N-(β-D-glucopyranosyl)-5-(naphth-2-yl)-1,2,4-oxadiazol-3-carboxamide | 1453191-66-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(β-D-glucopyranosyl)-5-(naphth-2-yl)-1,2,4-oxadiazol-3-carboxamide
• 英文别名: 5-naphthalen-2-yl-N-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-1,2,4-oxadiazole-3-carboxamide
• CAS: 1453191-66-6
• 化学式: C₁₉H₁₉N₃O₇
• 分子量: 401.376
• InChiKey: JLQUEIHCMOTBJZ-ULPMNANESA-N

物化性质

• 熔点：
  254-258 °C
• 密度：
  1.60±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  158
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,3,4,6-tetra-O-acetyl-D-glucosyl-1-amine 在 吡啶 、 甲醇 、 盐酸羟胺 、 四丁基氟化铵 、 sodium methylate 作用下， 以 四氢呋喃 、 吡啶 、 氯仿 、 甲苯 为溶剂， 反应 218.5h， 生成 N-(β-D-glucopyranosyl)-5-(naphth-2-yl)-1,2,4-oxadiazol-3-carboxamide
  参考文献：
  名称：

  Synthesis, enzyme kinetics and computational evaluation of N-(β-d-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors

  摘要：

  All possible isomers of N-beta-D-glucopyranosyl aryl-substituted oxadiazolecarboxamides were synthesised. O-Peracetylated N-cyanocarbonyl-beta-D-glucopyranosylamine was transformed into the corresponding N-glucosyl tetrazole-5-carboxamide, which upon acylation gave N-glucosyl 5-ary1-1,3,4-oxadiazole-2-carboxamides. The nitrite group of the N-cyanocarbonyl derivative was converted to amidoxime which was ring closed by acylation to N-glucosyl 5-aryl-1,2,4-oxadiazole-3-carboxamides. A one-pot reaction of protected beta-D-glucopyranosylamine with oxalyl chloride and then with arenecarboxamidoximes furnished N-glucosyl 3-aryl-1,2,4-oxadiazole-5-carboxamides. Removal of the O-acetyl protecting groups by the Zemplen Method produced test compounds which were evaluated as inhibitors of glycogen phosphorylase. Best inhibitors of these series were N-(beta-D-glucopyranosyl) 5-(naphth-1-yl)-1,2,4-oxadiazol-3-carboxamide (K-i = 30 mu M), N-(beta-D-glucopyranosyl) 5-(naphth-2-y1)-1,3,4-oxadiazol-2-carboxamide (K-i= 33 mu M), and N-(beta-D-glucopyranosyl) 3-phenyl-1,2,4-oxadiazol-5-carboxamide (K-i= 104 mu M). ADMET property predictions revealed these compounds to have promising oral drug-like properties without any toxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.024

文献信息

• Synthesis, enzyme kinetics and computational evaluation of N-(β-d-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors
  作者：Mária Polyák、Gergely Varga、Bence Szilágyi、László Juhász、Tibor Docsa、Pál Gergely、Jaida Begum、Joseph M. Hayes、László Somsák

  DOI：10.1016/j.bmc.2013.07.024

  日期：2013.9

  All possible isomers of N-beta-D-glucopyranosyl aryl-substituted oxadiazolecarboxamides were synthesised. O-Peracetylated N-cyanocarbonyl-beta-D-glucopyranosylamine was transformed into the corresponding N-glucosyl tetrazole-5-carboxamide, which upon acylation gave N-glucosyl 5-ary1-1,3,4-oxadiazole-2-carboxamides. The nitrite group of the N-cyanocarbonyl derivative was converted to amidoxime which was ring closed by acylation to N-glucosyl 5-aryl-1,2,4-oxadiazole-3-carboxamides. A one-pot reaction of protected beta-D-glucopyranosylamine with oxalyl chloride and then with arenecarboxamidoximes furnished N-glucosyl 3-aryl-1,2,4-oxadiazole-5-carboxamides. Removal of the O-acetyl protecting groups by the Zemplen Method produced test compounds which were evaluated as inhibitors of glycogen phosphorylase. Best inhibitors of these series were N-(beta-D-glucopyranosyl) 5-(naphth-1-yl)-1,2,4-oxadiazol-3-carboxamide (K-i = 30 mu M), N-(beta-D-glucopyranosyl) 5-(naphth-2-y1)-1,3,4-oxadiazol-2-carboxamide (K-i= 33 mu M), and N-(beta-D-glucopyranosyl) 3-phenyl-1,2,4-oxadiazol-5-carboxamide (K-i= 104 mu M). ADMET property predictions revealed these compounds to have promising oral drug-like properties without any toxicity. (C) 2013 Elsevier Ltd. All rights reserved.