(S)-N-methyl-4-(3-methylmorpholino)-2-(4-nitrophenyl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carbothioamide | 1415797-59-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: (S)-N-methyl-4-(3-methylmorpholino)-2-(4-nitrophenyl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carbothioamide
• CAS: 1415797-59-9
• 化学式: C₂₀H₂₄N₆O₃S
• 分子量: 428.515
• InChiKey: KXCYXEQDXJHDPS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  96.66
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-N-methyl-4-(3-methylmorpholino)-2-(4-nitrophenyl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carbothioamide 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (S)-3-methyl-4-(7-(1-methyl-1H-imidazol-2-yl)-2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine
  参考文献：
  名称：

  Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

  摘要：

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.

  DOI：

  10.1021/ml3003132
• 作为产物：
  描述：

  (S)-3-methyl-4-(2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine 、 异硫氰酸甲酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以93%的产率得到(S)-N-methyl-4-(3-methylmorpholino)-2-(4-nitrophenyl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carbothioamide
  参考文献：
  名称：

  Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

  摘要：

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.

  DOI：

  10.1021/ml3003132