(4S,5R,6S,7R)-7-methyl-3-phenyl-4,5,6,7-tetrahydro-[1, 2,3]triazolo[1,5-a]pyridine-4,5,6-triol | 1573124-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4S,5R,6S,7R)-7-methyl-3-phenyl-4,5,6,7-tetrahydro-[1, 2,3]triazolo[1,5-a]pyridine-4,5,6-triol
• 英文别名: ethyl 1-phenyl-5-[(1S,2S,3S)-1,2,3-trihydroxybutyl]triazole-4-carboxylate
• CAS: 1573124-13-6
• 化学式: C₁₅H₁₉N₃O₅
• 分子量: 321.333
• InChiKey: KXYBHXXUHKZGGM-HERUPUMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 5-((4S,5S)-5-((S)-1-hydroxyethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-1-phenyl-1H-1,2,3-triazole-4-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以90%的产率得到(4S,5R,6S,7R)-7-methyl-3-phenyl-4,5,6,7-tetrahydro-[1, 2,3]triazolo[1,5-a]pyridine-4,5,6-triol
  参考文献：
  名称：

  Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors

  摘要：

  Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of L-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key beta-ketoester building block 4 prepared from L-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9 nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1 nM) over SGLT1 (IC50: 693.2 nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.077

文献信息

• Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors
  作者：Siddamal Reddy Putapatri、Abhinav Kanwal、Sanjay K. Banerjee、Srinivas Kantevari

  DOI：10.1016/j.bmcl.2014.01.077

  日期：2014.3

  Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of L-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key beta-ketoester building block 4 prepared from L-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9 nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1 nM) over SGLT1 (IC50: 693.2 nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations. (C) 2014 Elsevier Ltd. All rights reserved.