4-{[(2-{(2R)-2-methyl-4-[5-(1-methylethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl}pyrimidin-5-yl)oxy]methyl}pyridine-3-carbonitrile | 1272973-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{[(2-{(2R)-2-methyl-4-[5-(1-methylethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl}pyrimidin-5-yl)oxy]methyl}pyridine-3-carbonitrile
• 英文别名: (R)-4-((2-(4-(5-isopropyl-1,2,4-oxadiazol-3-yl)-2-methylpiperazin-1-yl)pyrimidin-5-yloxy)methyl)nicotinonitrile；4-[[2-[(2R)-2-methyl-4-(5-propan-2-yl-1,2,4-oxadiazol-3-yl)piperazin-1-yl]pyrimidin-5-yl]oxymethyl]pyridine-3-carbonitrile
• CAS: 1272973-32-6
• 化学式: C₂₁H₂₄N₈O₂
• 分子量: 420.474
• InChiKey: UNGZTVLHLKAKQE-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (R)-4-Boc-2-甲基哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 盐酸 、 正丁基锂 、 硼酸三异丙酯 、 偶氮二甲酸二异丙酯 、 盐酸羟胺 、 碳酸氢钠 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 丁腈 、 正己烷 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 35.33h， 生成 4-{[(2-{(2R)-2-methyl-4-[5-(1-methylethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl}pyrimidin-5-yl)oxy]methyl}pyridine-3-carbonitrile
  参考文献：
  名称：

  Therapeutic Agents 812

  摘要：

  公式I的化合物或其药用可接受的盐，制备这类化合物的方法，它们作为GPR119调节剂的用途，它们的治疗用途的方法，特别是在肥胖和糖尿病的治疗中，以及含有它们的药物组合物。

  公开号：

  US20110065706A1

文献信息

• Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation
  作者：James S. Scott、Alan M. Birch、Katy J. Brocklehurst、Anders Broo、Hayley S. Brown、Roger J. Butlin、David S. Clarke、Öjvind Davidsson、Anne Ertan、Kristin Goldberg、Sam D. Groombridge、Julian A. Hudson、David Laber、Andrew G. Leach、Philip A. MacFaul、Darren McKerrecher、Adrian Pickup、Paul Schofield、Per H. Svensson、Pernilla Sörme、Joanne Teague

  DOI：10.1021/jm300310c

  日期：2012.6.14

  G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.
• [EN] 4- (PYRIMIDIN-2-YL) -PIPERAZINE AND 4- (PYRIMIDIN-2-YL) -PIPERIDINE DERIVATIVES AS GPR119 MODULATORS<br/>[FR] DERIVES DE 4-(PYRIMIDIN-2-YL)-PIPERAZINE ET DE 4-(PYRIMIDIN-2-YL)-PIPERIDINE UTILISES EN TANT QUE MODULATEURS DU GPR119
  申请人：ASTRAZENECA AB

  公开号：WO2011030139A1

  公开（公告）日：2011-03-17

  A compound of formula (I) or a pharmaceutically acceptable salt thereof, processes for preparing such compounds, their use as GPR119 modulators, methods for their therapeutic use, particularly in the treatment of obesity and diabetes mellitus, and pharmaceutical compositions containing them.
• [EN] SYSTEMS AND METHODS FOR PREDICTING CARDIOTOXICITY OF MOLECULAR PARAMETERS OF A COMPOUND BASED ON MACHINE LEARNING ALGORITHMS<br/>[FR] SYSTÈMES ET PROCÉDÉS PERMETTANT DE PRÉDIRE LA CARDIOTOXICITÉ DE PARAMÈTRES MOLÉCULAIRES D'UN COMPOSÉ SUR LA BASE D'ALGORITHMES D'APPRENTISSAGE MACHINE
  申请人：UTI LIMITED PARTNERSHIP

  公开号：WO2016201575A1

  公开（公告）日：2016-12-22

  Systems and methods are provided for predicting cardiotoxicity of molecular parameters of a compound. A computer can provide as input to a machine learning algorithm the molecular parameters of the compound. The molecular parameters can include at least structural information about the compound. The machine learning algorithm can have been trained using respective molecular parameters of compounds known to have cardiotoxicity and of compounds known not to have cardiotoxicity. The computer can receive as output from the machine learning algorithm a representation of the predicted cardiotoxicity of each molecular parameter of at least a subset of the molecular parameters of the compound.
• Therapeutic Agents 812
  申请人：Birch Alan Martin

  公开号：US20110065706A1

  公开（公告）日：2011-03-17

  A compound of formula I or a pharmaceutically acceptable salt thereof, processes for preparing such compounds, their use as GPR119 modulators, methods for their therapeutic use, particularly in the treatment of obesity and diabetes mellitus, and pharmaceutical compositions containing them.

  公式I的化合物或其药用可接受的盐，制备这类化合物的方法，它们作为GPR119调节剂的用途，它们的治疗用途的方法，特别是在肥胖和糖尿病的治疗中，以及含有它们的药物组合物。