1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl methanesulfonate | 1108164-40-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl methanesulfonate
• 英文别名: [1-[5-(Trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl] methanesulfonate
• CAS: 1108164-40-4
• 化学式: C₁₁H₁₄F₃N₃O₃S
• 分子量: 325.312
• InChiKey: WRKHMRCYEHDZCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-chloro-4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one 、 1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl methanesulfonate 在 二乙基偶氮二羧酸酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.27h， 以52%的产率得到5-chloro-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one
  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

• N-LINKED HETEROCYCLIC RECEPTOR AGONISTS FOR THE TREATMENT OF DIABETES AND METABOLIC DISORDERS
  申请人：Ma Jingyuan

  公开号：US20120322804A1

  公开（公告）日：2012-12-20

  Compounds and methods are provided for the treatment of, inter alia, Type II diabetes and other diseases associated with poor glycemic control.

  提供了化合物和方法，用于治疗类型II糖尿病和其他与糖代谢控制不良相关的疾病。
• N-AZACYCLIC SUBSTITUTED PYRROLE, IMIDAZOLE, TRIAZOLE AND TETRAZOLE DERIVATIVES AS AGONISTS OF THE RUP3 OR GPR119 FOR THE TREATMENT OF DIABETES AND METABOLIC DISORDERS
  申请人：Metabolex Inc.

  公开号：EP2185544A2

  公开（公告）日：2010-05-19
• N-AZACYCLIC SUBSTITUTED PYRROLE, PYRAZOLE, IMIDAZOLE, TRIAZOLE AND TETRAZOLE DERIVATIVES AS AGONISTS OF THE RUP3 OR GPR119 FOR THE TREATMENT OF DIABETES AND METABOLIC DISORDERS
  申请人：Cymabay Therapeutics, Inc.

  公开号：EP2185544B1

  公开（公告）日：2014-11-26
• US8183381B2
  申请人：——

  公开号：US8183381B2

  公开（公告）日：2012-05-22
• US8846675B2
  申请人：——

  公开号：US8846675B2

  公开（公告）日：2014-09-30