tert-butyl 4-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-methoxypyridin-2-yl)-piperazine-1-carboxylate | 1620099-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-methoxypyridin-2-yl)-piperazine-1-carboxylate
• CAS: 1620099-16-2
• 化学式: C₁₈H₂₃F₆N₃O₄
• 分子量: 459.389
• InChiKey: BGMBPOXPVZDTTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  31.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  75.13
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-methoxypyridin-2-yl)-piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  Small Molecule Disruptors of the Glucokinase–Glucokinase Regulatory Protein Interaction: 4. Exploration of a Novel Binding Pocket

  摘要：

  Structure-activity relationship investigations conducted at the 5-position of the N-pyridine ring of a series of N-arylsulfonyl-N'-2-pyridinyl-piperazines led to the identification of a novel bis-pyridinyl piperazine sulfonamide (51) that was a potent disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction. Analysis of the Xray cocrystal of compound 51 bound to hGKRP revealed that the 3-pyridine ring moiety occupied a previously unexplored binding pocket within the protein. Key features of this new binding mode included forming favorable contacts with the top face of the Ala27-Val28-Pro29 ("shelf region") as well as an edge-to-face interaction with the Tyr24 side chain. Compound Si was potent in both biochemical and cellular assays (IC50 = 0.005 mu M and EC50 = 0.205 mu M, respectively) and exhibited acceptable pharmacokinetic properties for in vivo evaluation. When administered to db/db mice (100 mg/kg, po), compound 51 demonstrated a robust pharmacodynamic effect and significantly reduced blood glucose levels up to 6 h postdose.

  DOI：

  10.1021/jm5001979
• 作为产物：
  描述：

  6-氯-5-甲氧基烟酸 在 草酰氯 、 四甲基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.17h， 生成 tert-butyl 4-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-methoxypyridin-2-yl)-piperazine-1-carboxylate
  参考文献：
  名称：

  Small Molecule Disruptors of the Glucokinase–Glucokinase Regulatory Protein Interaction: 4. Exploration of a Novel Binding Pocket

  摘要：

  Structure-activity relationship investigations conducted at the 5-position of the N-pyridine ring of a series of N-arylsulfonyl-N'-2-pyridinyl-piperazines led to the identification of a novel bis-pyridinyl piperazine sulfonamide (51) that was a potent disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction. Analysis of the Xray cocrystal of compound 51 bound to hGKRP revealed that the 3-pyridine ring moiety occupied a previously unexplored binding pocket within the protein. Key features of this new binding mode included forming favorable contacts with the top face of the Ala27-Val28-Pro29 ("shelf region") as well as an edge-to-face interaction with the Tyr24 side chain. Compound Si was potent in both biochemical and cellular assays (IC50 = 0.005 mu M and EC50 = 0.205 mu M, respectively) and exhibited acceptable pharmacokinetic properties for in vivo evaluation. When administered to db/db mice (100 mg/kg, po), compound 51 demonstrated a robust pharmacodynamic effect and significantly reduced blood glucose levels up to 6 h postdose.

  DOI：

  10.1021/jm5001979