tert-butyl 3-(((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yl)oxy)methyl)pyrrolidine-1-carboxylate | 1104443-04-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 3-(((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yl)oxy)methyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl 3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylate；Tert-butyl 3-[[1-(4-methylsulfonylphenyl)-2-oxopyridin-4-yl]oxymethyl]pyrrolidine-1-carboxylate
• CAS: 1104443-04-0
• 化学式: C₂₂H₂₈N₂O₆S
• 分子量: 448.54
• InChiKey: MCWZMPWKCGJYKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yl)oxy)methyl)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 3-[[1-(4-Methylsulfonylphenyl)-2-oxopyridin-4-yl]oxymethyl]pyrrolidine-1-carboxylic acid
  参考文献：
  名称：

  Discovery of 5-Chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an Antidiabetic Clinical Candidate Targeting GPR119

  摘要：

  G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic beta-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the gastrointestinal tract. This dual mechanism of action has generated significant interest in the discovery of small molecule GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, we describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 (42) was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of 42 in a single ascending dose study in normal healthy humans showed a dose dependent increase in exposure and a trend toward increased total GLP-1 plasma levels.

  DOI：

  10.1021/jm501175v
• 作为产物：
  描述：

  1-Boc-3-羟甲基吡咯烷 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 tert-butyl 3-(((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yl)oxy)methyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of 5-Chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an Antidiabetic Clinical Candidate Targeting GPR119

  摘要：

  G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic beta-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the gastrointestinal tract. This dual mechanism of action has generated significant interest in the discovery of small molecule GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, we describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 (42) was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of 42 in a single ascending dose study in normal healthy humans showed a dose dependent increase in exposure and a trend toward increased total GLP-1 plasma levels.

  DOI：

  10.1021/jm501175v

文献信息

• PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS
  申请人：Wacker Dean A.

  公开号：US20090023702A1

  公开（公告）日：2009-01-22

  Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.

  提供了一些新的化合物，它们是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR 119 G蛋白偶联受体调节剂疗法的疾病方面非常有用。这些新的化合物具有结构式I或结构式IA。
• US8003796B2
  申请人：——

  公开号：US8003796B2

  公开（公告）日：2011-08-23
• US8232404B2
  申请人：——

  公开号：US8232404B2

  公开（公告）日：2012-07-31
• US8513424B2
  申请人：——

  公开号：US8513424B2

  公开（公告）日：2013-08-20
• [EN] PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR GPR119 COUPLÉ À LA PROTÉINE G PYRIDONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009012275A1

  公开（公告）日：2009-01-22

  Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula (I) or Formula (IA).