isopropyl 9-anti-hydroxy-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate | 1269515-60-7

• 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: isopropyl 9-anti-hydroxy-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
• 英文别名: isopropyl 9-anti-hydroxy-3-oxa-7-azabicyclo[3.3.1]nonane
• CAS: 1269515-60-7
• 化学式: C₁₁H₁₉NO₄
• 分子量: 229.276
• InChiKey: CTTJBHDQSKQMBQ-ILWJIGKKSA-N

物化性质

• 沸点：
  366.0±42.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.47
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  59.0
• 氢给体数：
  1.0
• 氢受体数：
  4.0

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 、 isopropyl 9-anti-hydroxy-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate 在 sodium hexamethyldisilazane 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.3h， 以51%的产率得到isopropyl 9-anti-({5-methyl-6-[(2-methylpyridin-3-yl)oxy]-pyrimidin-4-yl}oxy)-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
  参考文献：
  名称：

  Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response

  摘要：

  The synthesis and properties of the bridged piperidine (oxaazabicyclo) compounds 8, 9, and 11 are described. A conformational analysis of these structures is compared with the representative GPR119 ligand 1. These results and the differences in agonist pharmacology are used to formulate a conformation-based hypothesis to understand activation of the GPR119 receptor. We also show for these structures that the agonist pharmacology in rat masks the important differences in human pharmacology.

  DOI：

  10.1021/jm200003p
• 作为产物：
  描述：

  3-oxa-7-azabicyclo[3.3.1]nonan-9-ol 、 氯甲酸异丙酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 14.0h， 以1.34 g的产率得到isopropyl 9-syn-hydroxy-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
  参考文献：
  名称：

  Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response

  摘要：

  The synthesis and properties of the bridged piperidine (oxaazabicyclo) compounds 8, 9, and 11 are described. A conformational analysis of these structures is compared with the representative GPR119 ligand 1. These results and the differences in agonist pharmacology are used to formulate a conformation-based hypothesis to understand activation of the GPR119 receptor. We also show for these structures that the agonist pharmacology in rat masks the important differences in human pharmacology.

  DOI：

  10.1021/jm200003p

文献信息

• 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