1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate | 1101873-46-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate
• 英文别名: 5-Propylpyrimidin-2-ylpiperidin-4-yl methanesulfonate；[1-(5-propylpyrimidin-2-yl)piperidin-4-yl] methanesulfonate
• CAS: 1101873-46-4
• 化学式: C₁₃H₂₁N₃O₃S
• 分子量: 299.394
• InChiKey: XZTSFKNVDRQHOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate 在 copper(l) iodide 、 8-羟基喹啉 、 potassium carbonate 、 caesium carbonate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.42h， 生成 5-chloro-1-(4-(methylsulfonyl)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
• 作为产物：
  描述：

  2-氯-5-正丙基嘧啶 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 3.0h， 生成 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate
  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
• 作为试剂：
  描述：

  1-(5-propylpyrimidin-2-yl)piperidin-4-ol 、 三乙胺 、 甲基磺酰氯 在 水 、 二氯甲烷 、 碳酸氢钠 、 Brine 、 Sodium sulfate-III 、 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以to give the desired product 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate (21 g, 70.1 mmol, 96% yield) as yellow solid的产率得到1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate
  参考文献：
  名称：

  Pyridone GPR119 G protein-coupled receptor agonists

  摘要：

  提供了新型化合物，其为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GPR119 G蛋白偶联受体调节剂疗法的疾病方面具有用途。这些新型化合物具有结构式I或结构式IA。

  公开号：

  US08003796B2

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。
• [EN] PYRIDONE AND PYRIDAZONE ANALOGUES AS GPR119 MODULATORS<br/>[FR] ANALOGUES DE PYRIDONE ET DE PYRIDAZONE COMME MODULATEURS DE GPR119
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010009183A1

  公开（公告）日：2010-01-21

  Novel compounds of structure Formula (I) or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein Z, R1, R2, R21, T1, T2, T3 and T4 are defined herein, 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. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  提供结构式（I）或其对映体、顺反异构体或药用可接受盐的新化合物，其中Z、R1、R2、R21、T1、T2、T3和T4在此定义，这些化合物是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GPR119 G蛋白偶联受体调节剂治疗的疾病方面是有用的。因此，该公开还涉及包含这些新化合物的组合物和使用任何这些新化合物或包含任何这种新化合物的组合物治疗与GPR119 G蛋白偶联受体活性相关的疾病或症状的方法。
• 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。
• PYRIDONE AND PYRIDAZONE ANALOGUES AS GPR119 MODULATORS
  申请人：Bristol-Myers Squibb Company

  公开号：US20130131074A1

  公开（公告）日：2013-05-23

  Novel compounds of structure Formula I: or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein Z, R 1 , R 2 , R 21 , T 1 , T 2 , T 3 and T 4 are defined herein, 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. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  提供了结构式I的新化合物，或其对映异构体、非对映异构体或制药上可接受的盐，其中Z、R1、R2、R21、T1、T2、T3和T4在此定义。这些化合物是GPR119 G蛋白偶联受体调节剂。 GPR119 G蛋白偶联受体调节剂可用于治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病的进展。因此，本公开还涉及包含这些新化合物的组合物以及使用任何这些新化合物或包含任何这些新化合物的组合物治疗与GPR119 G蛋白偶联受体活性相关的疾病或病症的方法。