tert-butyl 4-((7-(4-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate | 1416272-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: tert-butyl 4-((7-(4-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[7-(4-bromophenyl)pyrrolo[2,3-d]pyrimidin-4-yl]oxypiperidine-1-carboxylate；tert-butyl 4-[7-(4-bromophenyl)pyrrolo[2,3-d]pyrimidin-4-yl]oxypiperidine-1-carboxylate
• CAS: 1416272-92-8
• 化学式: C₂₂H₂₅BrN₄O₃
• 分子量: 473.369
• InChiKey: AJFRRWPYKZYULE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((7-(4-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate 、 sodium methansulfinate 在 copper(l) iodide 、 L-脯氨酸 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 以84%的产率得到tert-butyl 4-((7-(4-(methylsulfonyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a
• 作为产物：
  描述：

  4-氯吡咯并嘧啶 在 potassium phosphate 、 copper(l) iodide 、 (1R,2R)-1,2-diaminocyclohexane 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 tert-butyl 4-((7-(4-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a