tert-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)-phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate | 1339944-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)-phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate
• 英文别名: t-Butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate；tert-butyl 4-[5-chloro-1-(2-fluoro-4-methylsulfonylphenyl)-2-oxopyridin-4-yl]oxypiperidine-1-carboxylate
• CAS: 1339944-38-5
• 化学式: C₂₂H₂₆ClFN₂O₆S
• 分子量: 500.976
• InChiKey: MXNSGJUSHWPIKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  6
• 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：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)-phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate 在 盐酸 作用下， 以 水 为溶剂， 反应 0.25h， 以100%的产率得到5-chloro-1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one hydrogen chloride
  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：

  tert-butyl 4-((5-chloro-2-oxo-1,2-dihydropyridin-4-yl)oxy)-piperidine-1-carboxylate 以 吡啶 、 N-甲基吡咯烷酮 为溶剂， 反应 12.0h， 生成 tert-butyl 4-(5-chloro-1-(2-fluoro-4-(methylsulfonyl)-phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate
  参考文献：
  名称：

  PYRIMIDINYLPIPERIDINYLOXYPYRIDINONE ANALOGUES AS GPR119 MODULATORS

  摘要：

  结构式I的新化合物：或其对映体、非对映体异构体或药用可接受盐，其中n1、R1、R2、R3和R4在此处定义，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症状的方法。

  公开号：

  US20110251221A1

文献信息

• [EN] PYRIMIDINYLPIPERIDINYLOXYPYRIDINONE ANALOGUES AS GPR119 MODULATORS<br/>[FR] COMPOSÉS ANALOGUES DE LA PYRIMIDINYLPIPÉRIDINYLOXYPYRIDINONE COMME MODULATEURS DU GPR119
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011127106A1

  公开（公告）日：2011-10-13

  Novel compounds of structure Formula (I) or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein n1, R1, R2, R3 and R4 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）或其对映异构体、顺反异构体或药学上可接受的盐的新化合物，其中n1、R1、R2、R3和R4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，本文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来治疗与GPR119 G蛋白偶联受体活性相关的疾病或病症的方法。
• Pyrimidinylpiperidinyloxypyridinone analogues as GPR119 modulators
  申请人：Wacker Dean

  公开号：US08415367B2

  公开（公告）日：2013-04-09

  Novel compounds of structure Formula I: or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein n1, R1, R2, R3 and R4 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、顺反异构体或药物可接受的盐，其中n1、R1、R2、R3和R4的定义在此处，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，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来治疗与GPR119 G蛋白偶联受体活性相关的疾病或病况的方法。
• EP2556069B1
  申请人：——

  公开号：EP2556069B1

  公开（公告）日：2015-04-01
• US8415367B2
  申请人：——

  公开号：US8415367B2

  公开（公告）日：2013-04-09
• Design, Synthesis and In‐Silico Studies of Piperidine‐Dihydropyridine Hybrids as Anticancer Agents
  作者：Swathi Rejinthala、Srinivas Endoori、Vishnu Thumma、T. Mondal

  DOI：10.1002/cbdv.202301456

  日期：2024.4

  In this study, we designed, synthesized and characterized a novel series of piperidine‐dihydropyridine hybrid compounds and characterized them by ¹H‐NMR, ¹³C NMR, mass spectrometry (MS), and elemental analysis. Subsequently, we assessed their in vitro anticancer potentials against the human breast adenocarcinoma cell line MCF‐7 and the lung cancer cell line A‐549. Several of these compounds demonstrated significant activity, with IC₅₀ values ranging from 15.94 μM to 48.04 μM for A‐549 and 24.68 μM to 59.12 μM for MCF‐7, when compared to the reference drug Cisplatin.Notably, a compound featuring a 3‐fluoro substitution in the carboxamide series exhibited robust inhibitory effects, with an IC₅₀ of 15.94±0.201 μM against A‐549 cells and an IC₅₀ of 22.12±0.213 μM against MCF‐7 cells, respectively. Additionally, a compound containing a cyclobutyl ring displayed potent activity, with an IC₅₀ of 16.56±0.125 μM against A‐549 and an IC₅₀ of 24.68±0.217 μM against MCF‐7 cells, respectively. Furthermore, molecular docking studies against the Epidermal Growth Factor Receptor (EGFR) (PDB ID: 2J6M) revealed favourable binding scores and interactions, suggesting their potential as promising candidates for further investigation in the context of anticancer drug development.