(R)-2-(4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methylpiperazin-1-yl)pyrimidin-5-ol | 1379522-63-0

• 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: (R)-2-(4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methylpiperazin-1-yl)pyrimidin-5-ol
• CAS: 1379522-63-0
• 化学式: C₁₄H₁₈N₆O₂
• 分子量: 302.336
• InChiKey: WVMZNLPDFRHHRT-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.16
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.41
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-氯甲基-3-氰基吡啶 、 (R)-2-(4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methylpiperazin-1-yl)pyrimidin-5-ol 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 70.0h， 以48%的产率得到4-[({2-[(2R)-4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methylpiperazin-1-yl]pyrimidin-5-yl}oxy)methyl]pyridine-3-carbonitrile
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm300310c
• 作为产物：
  描述：

  (R)-4-Boc-2-甲基哌嗪 在 盐酸 、 sodium peroxoborate tetrahydrate 、 potassium acetate 、 palladium diacetate 、 碳酸氢钠 、 potassium carbonate 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 127.0h， 生成 (R)-2-(4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methylpiperazin-1-yl)pyrimidin-5-ol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm300310c