1-(4-aminofurazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]-triazole-4-carboxylic acid | 352446-61-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(4-aminofurazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]-triazole-4-carboxylic acid
• 英文别名: 1-(4-Amino-1,2,5-oxadiazol-3-yl)-5-(pyrrolidin-1-ium-1-ylmethyl)triazole-4-carboxylate
• CAS: 352446-61-8
• 化学式: C₁₀H₁₃N₇O₃
• mdl: MFCD02130400
• 分子量: 279.258
• InChiKey: PJPZKZPMZWJYAO-UHFFFAOYSA-N

物化性质

• 沸点：
  555.2±58.0 °C(Predicted)
• 密度：
  1.90±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-(2-氨基乙基)吡啶 、 1-(4-aminofurazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]-triazole-4-carboxylic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以78%的产率得到1-(4-Amino-furazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]triazole-4-carboxylic acid (2-pyridin-4-yl-ethyl)-amide
  参考文献：
  名称：

  Synthesis and in Vitro Characterization of 1-(4-Aminofurazan-3-yl)-5-dialkylaminomethyl-1H-[1,2,3]triazole-4-carboxylic Acid Derivatives. A New Class of Selective GSK-3 Inhibitors

  摘要：

  A novel class of GSK-3 inhibitors with favorable water solubility was identified in a HTS screen. SAR studies identified bioisosteric structural moieties in this class of compounds. The compounds were tested in a GSK-3 inhibition assay at 100 muM ATP giving IC50's in the range from 0.1 to 10 muM. The compounds are ATP competitive inhibitors. They modulate glycogen metabolism and stimulate the accumulation of intracellular beta-catenin in whole cell assays with EC50's in the range from 2 to 18 muM and 4.5-44 muM, respectively. For selected compounds, only a 10-fold lower potency was obtained in cellular assays compared to the potency obtained for inhibition of the isolated enzyme, reflecting a good cell permeability of this compound class. At 10 muM of test compound a Mold stimulation of the glycogen synthesis in rat soleus muscle was obtained compared to the level of glycogen synthesis observed at 0.2 nM insulin. This stimulation of glycogen synthesis is comparable to the maximal stimulation by insulin itself.

  DOI：

  10.1021/jm021095d
• 作为产物：
  描述：

  1-(4-aminofurazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl ester 在 盐酸 作用下， 反应 8.0h， 生成 1-(4-aminofurazan-3-yl)-5-pyrrolidin-1-ylmethyl-1H-[1,2,3]-triazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and in Vitro Characterization of 1-(4-Aminofurazan-3-yl)-5-dialkylaminomethyl-1H-[1,2,3]triazole-4-carboxylic Acid Derivatives. A New Class of Selective GSK-3 Inhibitors

  摘要：

  A novel class of GSK-3 inhibitors with favorable water solubility was identified in a HTS screen. SAR studies identified bioisosteric structural moieties in this class of compounds. The compounds were tested in a GSK-3 inhibition assay at 100 muM ATP giving IC50's in the range from 0.1 to 10 muM. The compounds are ATP competitive inhibitors. They modulate glycogen metabolism and stimulate the accumulation of intracellular beta-catenin in whole cell assays with EC50's in the range from 2 to 18 muM and 4.5-44 muM, respectively. For selected compounds, only a 10-fold lower potency was obtained in cellular assays compared to the potency obtained for inhibition of the isolated enzyme, reflecting a good cell permeability of this compound class. At 10 muM of test compound a Mold stimulation of the glycogen synthesis in rat soleus muscle was obtained compared to the level of glycogen synthesis observed at 0.2 nM insulin. This stimulation of glycogen synthesis is comparable to the maximal stimulation by insulin itself.

  DOI：

  10.1021/jm021095d

文献信息

• [EN] FURAZANYL-TRIAZOLE DERIVATES FOR THE TREATMENT OF DISEASES<br/>[FR] DERIVES DE FURAZANYL-TRIAZOLE DESTINES AU TRAITEMENT DE MALADIES
  申请人：NOVO NORDISK AS

  公开号：WO2002032896A1

  公开（公告）日：2002-04-25

  Pharmaceutical compositions comprising 1-(furazanyl-3-yl)-[1,2,3]triazole derivatives of the general formula (I) wherein the meanings of R?1, R2, R3, R4, R5¿ and n are as given in the description, for the treatment and/or prevention of disorders and diseases, wherein an inhibition of GSK-3 (glycogen synthase kinase-3) is beneficial, especially Alzheimer's disease, bipolar disorder, IGT (impaired glucose tolerance), Type 1 diabetes, Type 2 diabetes and obesity.
• Synthesis and in Vitro Characterization of 1-(4-Aminofurazan-3-yl)-5-dialkylaminomethyl-1<i>H</i>-[1,2,3]triazole-4-carboxylic Acid Derivatives. A New Class of Selective GSK-3 Inhibitors
  作者：Preben H. Olesen、Anders R. Sørensen、Birgitte Ursø、Peter Kurtzhals、Andrew N. Bowler、Ulrich Ehrbar、Bo F. Hansen

  DOI：10.1021/jm021095d

  日期：2003.7.1

  A novel class of GSK-3 inhibitors with favorable water solubility was identified in a HTS screen. SAR studies identified bioisosteric structural moieties in this class of compounds. The compounds were tested in a GSK-3 inhibition assay at 100 muM ATP giving IC50's in the range from 0.1 to 10 muM. The compounds are ATP competitive inhibitors. They modulate glycogen metabolism and stimulate the accumulation of intracellular beta-catenin in whole cell assays with EC50's in the range from 2 to 18 muM and 4.5-44 muM, respectively. For selected compounds, only a 10-fold lower potency was obtained in cellular assays compared to the potency obtained for inhibition of the isolated enzyme, reflecting a good cell permeability of this compound class. At 10 muM of test compound a Mold stimulation of the glycogen synthesis in rat soleus muscle was obtained compared to the level of glycogen synthesis observed at 0.2 nM insulin. This stimulation of glycogen synthesis is comparable to the maximal stimulation by insulin itself.