6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)pyridin-2(1H)-one | 1260088-66-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)pyridin-2(1H)-one
• 英文别名: 6-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilino]-1H-pyridin-2-one
• CAS: 1260088-66-1
• 化学式: C₁₇H₂₁BN₂O₃
• 分子量: 312.176
• InChiKey: QGRYQRVXBCUQIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-chloro-7,7-dimethyl-4-(3-methylmorpholino)-5,7-dihydrofuro[3,4-d]pyrimidine 、 6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)pyridin-2(1H)-one 在 四(三苯基膦)钯 、 potassium acetate 、 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 (S)-6-(4-(7,7-dimethyl-4-(3-methylmorpholino)-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)phenylamino)pyridin-2(1H)-one
  参考文献：
  名称：

  Potent, Selective, and Orally Bioavailable Inhibitors of Mammalian Target of Rapamycin (mTOR) Kinase Based on a Quaternary Substituted Dihydrofuropyrimidine

  摘要：

  A series of inhibitors of mTOR kinase based on a quaternary-substituted dihydrofuropyrimidine was designed and synthesized. The most potent compounds in this series inhibited mTOR kinase with K-i < 1.0 nM and were highly (>100x) selective for mTOR over the closely related PI3 kinases. Compounds in this series showed inhibition of the pathway and antiproliferative activity in cell-based assays. Furthermore, these compounds had excellent mouse PK, and showed a robust PK-PD relationship in a mouse model of cancer.

  DOI：

  10.1021/jm200215y

文献信息

• OXO-HETEROCYCLE FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Bergeron Philippe

  公开号：US20100331305A1

  公开（公告）日：2010-12-30

  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).

  本发明涉及式I的化合物，包括其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，这些化合物对调节PIKK相关激酶信号传导，例如mTOR，并用于治疗通过PIKK信号通路失调（例如mTOR）至少部分介导的疾病（例如癌症）是有用的。