6-(4-hydroxyphenyl)-4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-(4-hydroxyphenyl)-4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one
• 英文别名: 6-(4-Hydroxyphenyl)-4-phenyl-1,4-benzoxazin-3-one；6-(4-hydroxyphenyl)-4-phenyl-1,4-benzoxazin-3-one
• 化学式: C₂₀H₁₅NO₃
• 分子量: 317.344
• InChiKey: MJERVHJXUSZIAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-4-溴苯酚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 copper diacetate 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 6-(4-hydroxyphenyl)-4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one
  参考文献：
  名称：

  Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors

  摘要：

  PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of molecules with skeleton of 4-phenyl-2H-benzo[b] [1,4]oxazin-3(4H)-one were designed and synthesized targeting this pathway. Bioassays showed that, among all the molecules, 8d-1 was a pan-class I PI3K/mTOR inhibitor with an IC50 of 0.63 nM against PI3K alpha. In a wide panel of protein kinases assays, no off-target interactions of 8d-1 were identified. 8d-1 was orally available, and displayed favorable pharmacokinetic parameters in mice (oral bioavailability of 24.1%). In addition, 8d-1 demonstrated significant efficiency in Hela/A549 tumor xenograft models (TGI of 87.7% at dose of 50 mg/kg in Hela model) without causing significant weight loss and toxicity during 30 days treatment. Based on the bioassays, compound 8d-1 could be used as an anti-cancer drug candidate. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.06.021

文献信息

• Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors
  作者：Guoyi Yan、Chunlan Pu、Suke Lan、Xinxin Zhong、Meng Zhou、Xueyan Hou、Jie Yang、Huifang Shan、Lifeng Zhao、Rui Li

  DOI：10.1016/j.ejmech.2019.06.021

  日期：2019.9

  PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of molecules with skeleton of 4-phenyl-2H-benzo[b] [1,4]oxazin-3(4H)-one were designed and synthesized targeting this pathway. Bioassays showed that, among all the molecules, 8d-1 was a pan-class I PI3K/mTOR inhibitor with an IC50 of 0.63 nM against PI3K alpha. In a wide panel of protein kinases assays, no off-target interactions of 8d-1 were identified. 8d-1 was orally available, and displayed favorable pharmacokinetic parameters in mice (oral bioavailability of 24.1%). In addition, 8d-1 demonstrated significant efficiency in Hela/A549 tumor xenograft models (TGI of 87.7% at dose of 50 mg/kg in Hela model) without causing significant weight loss and toxicity during 30 days treatment. Based on the bioassays, compound 8d-1 could be used as an anti-cancer drug candidate. (C) 2019 Published by Elsevier Masson SAS.