(S)-1-phenoxycarbonyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)thiourea | 1207369-94-5

• 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)-1-phenoxycarbonyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)thiourea
• 英文别名: phenyl N-[[4-[4-[(3S)-3-methylmorpholin-4-yl]-7-pyrimidin-2-yl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-2-yl]phenyl]carbamothioyl]carbamate
• CAS: 1207369-94-5
• 化学式: C₃₀H₃₀N₈O₃S
• 分子量: 582.686
• InChiKey: VMVDWLZOZJXOHE-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-1-phenoxycarbonyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)thiourea 、 甲基肼 以 四氢呋喃 为溶剂， 生成 (S)-1-methyl-N-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenylcarbamothioyl)hydrazinecarboxamide
  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)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 4.17h， 生成 (S)-1-phenoxycarbonyl-3-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)thiourea
  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

文献信息

• PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Bergeron Philippe

  公开号：US20100069357A1

  公开（公告）日：2010-03-18

  Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

  本发明涉及I式化合物，包括其立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，其对调节PIKK相关激酶信号传导，例如mTOR，并用于治疗至少部分由PIKK信号通路失调介导的疾病（例如癌症）具有用处。
• US8163763B2
  申请人：——

  公开号：US8163763B2

  公开（公告）日：2012-04-24