7-(4-bromophenyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine | 1416272-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 7-(4-bromophenyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 7-(4-Bromophenyl)-4-chloropyrrolo[2,3-d]pyrimidine；7-(4-bromophenyl)-4-chloropyrrolo[2,3-d]pyrimidine
• CAS: 1416272-91-7
• 化学式: C₁₂H₇BrClN₃
• 分子量: 308.565
• InChiKey: GHMYLMIMKHBBOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-(4-bromophenyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine 在 copper(l) iodide 、 caesium carbonate 、 L-脯氨酸 、 sodium hydroxide 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 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：

  对溴碘苯 、 4-氯吡咯并嘧啶 在 potassium phosphate 、 copper(l) iodide 、 (1R,2R)-1,2-diaminocyclohexane 作用下， 反应 15.0h， 以30%的产率得到7-(4-bromophenyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine
  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

文献信息

• Discovery of 6,7-Dihydro-5<i>H</i>-pyrrolo[2,3-<i>a</i>]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists
  作者：Subba R. Katamreddy、Andrew J. Carpenter、Carina E. Ammala、Eric E. Boros、Ron L. Brashear、Celia P. Briscoe、Sarah R. Bullard、Richard D. Caldwell、Christopher R. Conlee、Dallas K. Croom、Shane M. Hart、Dennis O. Heyer、Paul R. Johnson、Jennifer A. Kashatus、Doug J. Minick、Gregory E. Peckham、Sean A. Ross、Shane G. Roller、Vicente A. Samano、Howard R. Sauls、Sarva M. Tadepalli、James B. Thompson、Yun Xu、James M. Way

  DOI：10.1021/jm301404a

  日期：2012.12.27

  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.