1-(5-氯嘧啶-2-基)哌啶-4-醇 | 1108164-37-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-(5-氯嘧啶-2-基)哌啶-4-醇
• 英文名称: 1-(5-chloropyrimidin-2-yl)piperidin-4-ol
• CAS: 1108164-37-9
• 化学式: C₉H₁₂ClN₃O
• 分子量: 213.667
• InChiKey: BEQLIYXYBCBOFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  49.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 储存条件：
  应存于室温、密封且干燥的环境中。

反应信息

• 作为反应物：
  描述：

  1-(5-氯嘧啶-2-基)哌啶-4-醇 在 sodium hydride 、 diisopropyl (E)-azodicarboxylate 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 34.5h， 生成 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(3-fluoro-4-(methylsulfonyl)phenyl)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：

  4-羟基哌啶 、 5-氯-2-碘嘧啶 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以87%的产率得到1-(5-氯嘧啶-2-基)哌啶-4-醇
  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。
• 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。
• 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。
• Nicotinic acids: Liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy
  作者：David A. Powell、W. Cameron Black、Kelly Bleasby、Chi-Chung Chan、Denis Deschenes、Marc Gagnon、Rob Gordon、Jocelyne Guay、Sebastien Guiral、Michael J. Hafey、Zheng Huang、Elise Isabel、Yves Leblanc、Angela Styhler、Li-Jing Xu、Lei Zhang、Renata M. Oballa

  DOI：10.1016/j.bmcl.2011.10.040

  日期：2011.12

  An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity. (C) 2011 Elsevier Ltd. All rights reserved.
• 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