tert-butyl 4-(2-{[4-(methylsulfonyl)benzyl]oxy}pyrimidin-5-yl)piperazine-1-carboxylate | 1379522-30-1

• 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: tert-butyl 4-(2-{[4-(methylsulfonyl)benzyl]oxy}pyrimidin-5-yl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-[2-[(4-methylsulfonylphenyl)methoxy]pyrimidin-5-yl]piperazine-1-carboxylate
• CAS: 1379522-30-1
• 化学式: C₂₁H₂₈N₄O₅S
• 分子量: 448.543
• InChiKey: ZJBKMINXKKATNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-甲砜基苯甲醇 在 sodium hydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.75h， 生成 tert-butyl 4-(2-{[4-(methylsulfonyl)benzyl]oxy}pyrimidin-5-yl)piperazine-1-carboxylate
  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