1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one | 1101873-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one
• 英文别名: 4-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]oxy-1-[4-(1,2,4-triazol-1-yl)phenyl]pyridin-2-one
• CAS: 1101873-48-6
• 化学式: C₂₅H₂₇N₇O₂
• 分子量: 457.535
• InChiKey: RNJYVMGLFSAETA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  89.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate 在 copper(l) iodide 、 8-羟基喹啉 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 3.5h， 生成 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(1-(5-propylpyrimidin-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

• METHOD FOR MODULATING GPR119 G PROTEIN-COUPLED RECEPTOR AND SELECTED COMPOUNDS
  申请人：Wacker Dean A.

  公开号：US20090042919A1

  公开（公告）日：2009-02-12

  A method of modulating the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound of Formula I or Formula IA and, optionally, an additional therapeutic agent.

  一种调节GPR119 G蛋白偶联受体活性的方法，包括向需要治疗的哺乳动物患者施用至少一种公式I或公式IA化合物的治疗有效量，以及可选的其他治疗剂。
• Method for modulating GPR119 G protein-coupled receptor and selected compounds
  申请人：Bristol-Myers Squibb Company

  公开号：US08178561B2

  公开（公告）日：2012-05-15

  A method of modulating the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound of Formula I or Formula IA and, optionally, an additional therapeutic agent.

  一种调节GPR119 G蛋白偶联受体活性的方法，包括向需要治疗的哺乳动物患者施用至少一种公式I或公式IA化合物的治疗有效剂量，以及可选的其他治疗药物。
• US7928230B2
  申请人：——

  公开号：US7928230B2

  公开（公告）日：2011-04-19
• US8178561B2
  申请人：——

  公开号：US8178561B2

  公开（公告）日：2012-05-15
• [EN] METHOD FOR MODULATING GPR119 G PROTEIN-COUPLED RECEPTOR AND SELECTED COMPOUNDS<br/>[FR] PROCÉDÉ DE MODULATION DE RÉCEPTEUR GPR119 DE LA PROTÉINE G ET COMPOSÉS SÉLECTIONNÉS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009012277A1

  公开（公告）日：2009-01-22

  A method of modulating the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (IA) and, optionally, an additional therapeutic agent.