N-[(2R,3S)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-2-[[methyl(methylsulfonyl)amino]methyl]-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-1-methylimidazole-4-sulfonamide | 1222472-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-[(2R,3S)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-2-[[methyl(methylsulfonyl)amino]methyl]-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-1-methylimidazole-4-sulfonamide
• CAS: 1222472-93-6
• 化学式: C₂₁H₃₁N₅O₇S₂
• 分子量: 529.638
• InChiKey: GSMCHHIMYMWGKU-MPGHIAIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  168
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 pyridine hydrofluoride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-[(2R,3S)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-2-[[methyl(methylsulfonyl)amino]methyl]-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-1-methylimidazole-4-sulfonamide
  参考文献：
  名称：

  Synthesis of a Novel Suppressor of β-Cell Apoptosis via Diversity-Oriented Synthesis

  摘要：

  The synthesis of a stereochemically diverse library of medium-sized rings accessible via a "build/couple/pair" strategy is described. Key aspects of the synthesis include SNAr cycloetherification of a linear amine template to afford eight stereoisomeric eight-membered lactams and subsequent solid-phase diversification of these scaffolds to yield a 6488-membered library. Screening of this compound collection in a cell-based assay for the suppression of cytokine-induced beta-cell apoptosis resulted in the identification of a small-molecule suppressor capable of restoring glucose-stimulated insulin secretion in a rat beta-cell line. The presence of all stereoisomers in the screening collection enabled preliminary determination of the structural and stereochemical requirements for cellular activity, while efficient follow-up chemistry afforded BRD0476 (probe ML187), which had an approximately 3-fold increase in activity. These results demonstrate the utility of diversity-oriented synthesis to probe discovery using cell-based screening and the importance of including stereochemical diversity in screening collections for the development of stereo/structure-activity relationships.

  DOI：

  10.1021/ml200120m