N-(2-chloro-5-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide | 1201844-49-6

• 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: N-(2-chloro-5-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide
• 英文别名: N-[2-chloro-5-(3-oxo-4H-1,4-benzoxazin-6-yl)pyridin-3-yl]-4-fluorobenzenesulfonamide
• CAS: 1201844-49-6
• 化学式: C₁₉H₁₃ClFN₃O₄S
• 分子量: 433.847
• InChiKey: YBIHJNHOIHMJJN-UHFFFAOYSA-N

物化性质

• 密度：
  1.529±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氯-3-氨基-5-溴吡啶 在 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 吡啶 、 potassium acetate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 36.0h， 生成 N-(2-chloro-5-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide
  参考文献：
  名称：

  [EN] INHIBITORS OF PI3 KINASE
  [FR] INHIBITEURS DE LA PI3 KINASE

  摘要：

  公开号：

  WO2009155121A3

文献信息

• INHIBITORS OF PI3 KINASE
  申请人：Bo Yunxin Y.

  公开号：US20110092504A1

  公开（公告）日：2011-04-21

  The present invention relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein Q, X 1 , X 2 , R 1 and Z are as defined herein.

  本发明涉及式（I）的化合物，或其药学上可接受的盐；使用该化合物治疗疾病或病症的方法，例如癌症；以及含有该化合物的制药组合物，其中Q、X1、X2、R1和Z的定义如本文所述。
• [EN] INHIBITORS OF PI3 KINASE<br/>[FR] INHIBITEURS DE LA PI3 KINASE
  申请人：AMGEN INC

  公开号：WO2009155121A3

  公开（公告）日：2010-02-18
• US8415376B2
  申请人：——

  公开号：US8415376B2

  公开（公告）日：2013-04-09
• 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.