4(5)-(2-naphthyl)-2-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)imidazole | 1430730-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4(5)-(2-naphthyl)-2-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)imidazole
• 英文别名: 4(5)-(2-naphthyl)-2-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)imidazole
• CAS: 1430730-99-6
• 化学式: C₄₇H₃₆N₂O₉
• 分子量: 772.811
• InChiKey: GCYRDQJDCJZFQS-QBLDGPCBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  58.0
• 可旋转键数：
  11.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  143.11
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4(5)-(2-naphthyl)-2-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)imidazole 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以77%的产率得到2-(β-D-glucopyranosyl)-4(5)-(2-naphthyl)imidazole
  参考文献：
  名称：

  4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase

  摘要：

  Inhibition of glycogen phosphorylases may lead to pharmacological treatments of diseases in which glycogen metabolism plays an important role: first of all in diabetes, but also in cardiovascular and tumorous disorders. C-(beta-D-Glucopyranosyl) isoxazole, pyrazole, thiazole, and imidazole type compounds were synthesized, and the latter showed the strongest inhibition against rabbit muscle glycogen phosphorylase b. Most efficient was 2-(beta-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole (11b, K-i = 31 nM) representing the best nanomolar glucose derived inhibitor of the enzyme.

  DOI：

  10.1021/acsmedchemlett.5b00361
• 作为产物：
  描述：

  C-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)formamidine 、 2-溴代-2-乙酰基萘 在 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 以10%的产率得到4(5)-(2-naphthyl)-2-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)imidazole
  参考文献：
  名称：

  4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase

  摘要：

  Inhibition of glycogen phosphorylases may lead to pharmacological treatments of diseases in which glycogen metabolism plays an important role: first of all in diabetes, but also in cardiovascular and tumorous disorders. C-(beta-D-Glucopyranosyl) isoxazole, pyrazole, thiazole, and imidazole type compounds were synthesized, and the latter showed the strongest inhibition against rabbit muscle glycogen phosphorylase b. Most efficient was 2-(beta-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole (11b, K-i = 31 nM) representing the best nanomolar glucose derived inhibitor of the enzyme.

  DOI：

  10.1021/acsmedchemlett.5b00361

文献信息

• Synthetic, enzyme kinetic, and protein crystallographic studies of C -β- d -glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase
  作者：Anastassia L. Kantsadi、Éva Bokor、Sándor Kun、George A. Stravodimos、Demetra S.M. Chatzileontiadou、Demetres D. Leonidas、Éva Juhász-Tóth、Andrea Szakács、Gyula Batta、Tibor Docsa、Pál Gergely、László Somsák

  DOI：10.1016/j.ejmech.2016.06.049

  日期：2016.11

  followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors

  Ç -β- d吡喃葡萄糖基吡咯在吡咯，2-的反应制备衍生物，和-吡咯-3-芳ö -peracetylatedβ- d吡喃葡萄糖基三氯乙酰亚胺酯，而2-（β- d得到吡喃葡萄糖基）吲哚通过使O-全苄基化的β- d-吡喃葡萄糖基乙炔与N-甲苯磺酰基-2-碘苯胺交叉偶联，然后自发闭环。通过使C反应，可以得到O-过苯甲酰化的2-（β- d-吡喃葡萄糖基）咪唑的改进合成方法-吡喃葡萄糖基甲酸酯与α-氨基酮。用糖原磷酸化酶（GP）的同工型分析去保护的化合物，以显示吡咯对兔肌肉GPb无活性。咪唑不仅是肌肉酶（a和b），而且是与药理相关的人肝GPa（ 4（5）-苯基的K i分别为156和26 nM，以及- （2-萘基）衍生物）。rmGPb-咪唑配合物的X射线晶体学研究揭示了强结合的结构特征，也可以解释对吡咯衍生物没有抑制作用。