4-氯-5-甲基-6-((2-甲基吡啶-3-基)氧基)嘧啶 | 930093-72-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-氯-5-甲基-6-((2-甲基吡啶-3-基)氧基)嘧啶
• 中文别名: 4-氯-5-甲基-6-(2-甲基吡啶-3-氧基)嘧啶
• 英文名称: 4-chloro-5-methyl-6-((2-methylpyridin-3-yl)oxy)pyrimidine
• 英文别名: 4-chloro-5-methyl-6-[(2-methylpyridin-3-yl)oxy]pyrimidine；4-chloro-5-methyl-6-(2-methyl-pyridin-3-yloxy)-pyrimidine；4-chloro-5-methyl-6-(2-methylpyridin-3-yl)oxypyrimidine
• CAS: 930093-72-4
• 化学式: C₁₁H₁₀ClN₃O
• 分子量: 235.673
• InChiKey: SLKKQWWYTQOOHM-UHFFFAOYSA-N

物化性质

• 沸点：
  342.7±42.0 °C(Predicted)
• 密度：
  1.279

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氯-5-甲基-6-((2-甲基吡啶-3-基)氧基)嘧啶 在 potassium tert-butylate 、 三氟乙酸 作用下， 生成 ethyl (1R,3s,5S)-3-((5-methyl-6-((2-methylpyridin-3-yl)oxy)pyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035
• 作为产物：
  描述：

  3-羟基-2-甲基吡啶 、 4,6-二氯-5-甲基嘧啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以76%的产率得到4-氯-5-甲基-6-((2-甲基吡啶-3-基)氧基)嘧啶
  参考文献：
  名称：

  [EN] BICYCLIC PIPERIDINE AND PIPERAZINE DERIVATIVES AS GPCR MODULATORS FOR THE TREATMENT OF OBESITY, DIABETES AND OTHER METABOLIC DISORDERS
  [FR] DÉRIVÉS DE PIPÉRIDINE ET DE PIPÉRAZINE BICYCLIQUES EN TANT QUE MODULATEURS DE RCPG POUR LE TRAITEMENT DE L'OBÉSITÉ, DU DIABÈTE ET D'AUTRES TROUBLES MÉTABOLIQUES

  摘要：

  本发明涉及双环哌啶和哌嗪衍生物，包括含有双环哌啶和哌嗪衍生物的组合物，以及使用双环哌啶和哌嗪衍生物治疗或预防患者的肥胖症、糖尿病、代谢性疾病、心血管疾病或与GPCR活性有关的疾病的方法。

  公开号：

  WO2010114957A1

文献信息

• [EN] BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'HÉTÉROCYCLES BICYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2010075273A1

  公开（公告）日：2010-07-01

  The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

  本发明涉及双环杂环衍生物，包含双环杂环衍生物的组合物，以及使用双环杂环衍生物治疗或预防患者的肥胖、糖尿病、代谢紊乱、心血管疾病或与GPCR活性相关的疾病的方法。
• [EN] GPR 119 MODULATORS<br/>[FR] MODULATEURS DE GPR 119
  申请人：PFIZER

  公开号：WO2013011402A1

  公开（公告）日：2013-01-24

  Compounds that modulate the activity of the G-protein-coupled receptor GPR119 and their uses in the treatment of diseases linked to the modulation of the G-protein- coupled receptor GPR119 in animals are described herein.

  本文描述了调节G蛋白偶联受体GPR119活性的化合物及其在治疗与动物中G蛋白偶联受体GPR119调节相关的疾病中的用途。
• Intrinsic Electrophilicity of a 4-Substituted-5-cyano-6-(2-methylpyridin-3-yloxy)pyrimidine Derivative: Structural Characterization of Glutathione Conjugates in Vitro
  作者：Amit S. Kalgutkar、Vincent Mascitti、Raman Sharma、Gregory W. Walker、Tim Ryder、Thomas S. McDonald、Yue Chen、Cathy Preville、Arindrajit Basak、Kim F. McClure、Jeffrey T. Kohrt、Ralph P. Robinson、Michael J. Munchhof、Peter Cornelius

  DOI：10.1021/tx100429x

  日期：2011.2.18

  toward reaction with glutathione. This observation suggests that the electron-withdrawing potential of the C5 cyano group serves to increase the electrophilicity of the C6 carbon (via stabilization of the transition state) and favors reaction with the nucleophilic thiol. The mechanistic insights gained from these studies should assist medicinal chemistry efforts toward the design of analogs that retain

  异丙基9-抗-[5-氰基-6-（2-甲基-吡啶-3-基氧基）-嘧啶-4-基氧基] -3-氧杂-7-氮杂-双环[3.3.1]壬烷-7-羧酸盐（1）代表来自G蛋白偶联受体119激动剂的主要化学系列的原型化合物，旨在治疗2型糖尿病。当化合物1与NADPH补充的人肝微粒体谷胱甘肽，二的存在硫醚偶联物温育M4- 1和M5- 1观察到。从微粒体温育NADPH的遗漏防止M5-的形成1但不M4- 1。M4-的形成1还辨别在温育1谷胱甘肽与人肝细胞溶质，部分纯化的谷胱甘肽转移酶，并在pH 7.4的磷酸盐缓冲液中。M4- 1被分离，并且它的结构由LC-MS / MS和NMR分析确定。质谱和NMR数据表明，M4- 1从6-（2-甲基吡啶-3-基氧基）基团的亲核置换中得到1通过谷胱甘肽。另外，质谱的研究显示，M5- 1是从上的单羟基化代谢物的类似位移反应而得1 ; 确定羟基化的区域化学是在异丙基上。伟大的令人感兴
• BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS MODULATORS OF THE ACTIVITY OF GPR119
  申请人：Xia Yan

  公开号：US20110212938A1

  公开（公告）日：2011-09-01

  The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

  本发明涉及双环杂环衍生物、包含双环杂环衍生物的组合物以及使用双环杂环衍生物治疗或预防患者的肥胖症、糖尿病、代谢紊乱、心血管疾病或与GPR119活性相关的疾病的方法。
• Modulators of Metabolism and the Treatment of Disorders Related Thereto
  申请人：Jones Robert M.

  公开号：US20100160359A1

  公开（公告）日：2010-06-24

  The present invention relates to 4-[5-methyl-6-(2-methyl-pyridin-3-yloxy)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester, pharmaceutically acceptable salts, solvates and hydrates thereof that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the treatment of metabolic-related disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及4-[5-甲基-6-(2-甲基吡啶-3-氧基)-嘧啶-4-氧基]-哌啶-1-羧酸异丙酯，其药学上可接受的盐、溶剂和水合物，它们是葡萄糖代谢调节剂。因此，本发明的化合物在代谢相关疾病和并发症的治疗中是有用的，例如糖尿病和肥胖症。