(2S,3S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-methylpentan-1-one | 1416956-35-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-methylpentan-1-one
• 英文别名: (2S,3S)-2-amino-1-[4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]piperazin-1-yl]-3-methylpentan-1-one
• CAS: 1416956-35-8
• 化学式: C₂₅H₃₃F₂N₉O₂
• 分子量: 529.593
• InChiKey: QGQJNXQVPVENJB-LPHOPBHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazine-1-carboxylate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.66h， 生成 (2S,3S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-methylpentan-1-one
  参考文献：
  名称：

  l-Aminoacyl-triazine Derivatives Are Isoform-Selective PI3Kβ Inhibitors That Target Nonconserved Asp862 of PI3Kβ

  摘要：

  A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3K beta. The compounds showed selectivity based upon stereochemistry with L-amino acyl derivatives preferring PI3K beta, while their D-congeners favored PI3K delta. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3K beta-selective inhibitors, distinguishing this class from other reported PI3K beta-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.

  DOI：

  10.1021/ml300336j

文献信息

• <scp>l</scp>-Aminoacyl-triazine Derivatives Are Isoform-Selective PI3Kβ Inhibitors That Target Nonconserved Asp862 of PI3Kβ
  作者：Jo-Anne Pinson、Zhaohua Zheng、Michelle S. Miller、David K. Chalmers、Ian G. Jennings、Philip E. Thompson

  DOI：10.1021/ml300336j

  日期：2013.2.14

  A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3K beta. The compounds showed selectivity based upon stereochemistry with L-amino acyl derivatives preferring PI3K beta, while their D-congeners favored PI3K delta. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3K beta-selective inhibitors, distinguishing this class from other reported PI3K beta-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.