1-(3-((2-phenylquinazolin-4-yl)amino)phenyl)ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-((2-phenylquinazolin-4-yl)amino)phenyl)ethanone
• 英文别名: 1-[3-(2-phenylquinazolin-4-ylamino)-phenyl]-ethanone；1-[3-(2-Phenyl-quinazolin-4-ylamino)-phenyl]-ethanone；1-[3-[(2-phenylquinazolin-4-yl)amino]phenyl]ethanone
• 化学式: C₂₂H₁₇N₃O
• mdl: MFCD02047127
• 分子量: 339.396
• InChiKey: IVEZQOPVGUKFEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 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：
  54.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-((2-phenylquinazolin-4-yl)amino)phenyl)ethanone 、 3-甲氧基苯甲醛 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以48%的产率得到(E)-3-(3-methoxyphenyl)-1-(3-((2-phenylquinazolin-4-yl)amino)phenyl)prop-2-en-1-one
  参考文献：
  名称：

  The combination of quinazoline and chalcone moieties leads to novel potent heterodimeric modulators of breast cancer resistance protein (BCRP/ABCG2)

  摘要：

  During the last decade it has been found that chalcones and quinazolines are promising inhibitors of ABCG2. The combination of these two scaffolds offers a new class of heterocyclic compounds with potentially high inhibitory activity against ABCG2. For this purpose we investigated 22 different heterodimeric derivatives. In this series only methoxy groups were used as substituents as these had been proven superior for inhibitory activity of chalcones. All compounds were tested for their inhibitory activity, specificity and cytotoxicity. The most potent ABCG2 inhibitor in this series showed an IC50 value of 0.19 mu M. It possesses low cytotoxicity (GI(50) = 93 mu M), the ability to reverse MDR and is nearly selective toward ABCG2. Most compounds containing dimethoxy groups showed slight activity against ABCB1 too. Among these three compounds (17,19 and 24) showed even higher activity toward ABCB1 than ABCG2. All inhibitors were further screened for their effect on basal ATPase activity. Although the basal ATPase activity was partially stimulated, the compounds were not transported by ABCG2. Thus, quinazoline-chalcones are a new class of effective ABCG2 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.067
• 作为产物：
  描述：

  2-苯基-4-[3H]喹唑啉酮 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 9.0h， 生成 1-(3-((2-phenylquinazolin-4-yl)amino)phenyl)ethanone
  参考文献：
  名称：

  The combination of quinazoline and chalcone moieties leads to novel potent heterodimeric modulators of breast cancer resistance protein (BCRP/ABCG2)

  摘要：

  During the last decade it has been found that chalcones and quinazolines are promising inhibitors of ABCG2. The combination of these two scaffolds offers a new class of heterocyclic compounds with potentially high inhibitory activity against ABCG2. For this purpose we investigated 22 different heterodimeric derivatives. In this series only methoxy groups were used as substituents as these had been proven superior for inhibitory activity of chalcones. All compounds were tested for their inhibitory activity, specificity and cytotoxicity. The most potent ABCG2 inhibitor in this series showed an IC50 value of 0.19 mu M. It possesses low cytotoxicity (GI(50) = 93 mu M), the ability to reverse MDR and is nearly selective toward ABCG2. Most compounds containing dimethoxy groups showed slight activity against ABCB1 too. Among these three compounds (17,19 and 24) showed even higher activity toward ABCB1 than ABCG2. All inhibitors were further screened for their effect on basal ATPase activity. Although the basal ATPase activity was partially stimulated, the compounds were not transported by ABCG2. Thus, quinazoline-chalcones are a new class of effective ABCG2 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.067

文献信息

• Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents
  作者：H. Cope、R. Mutter、W. Heal、C. Pascoe、P. Brown、S. Pratt、B. Chen

  DOI：10.1016/j.ejmech.2006.05.002

  日期：2006.10

  Transmissible spongiform encephalopathies (TSEs) are thought to arise from aggregation of a protease resistant protein denoted PrPSc, which is a misfolded isoform of the normal cellular prion protein PrPC. Using virtual high-throughput screening we have selected structures analogous to acridine, 2-methyquinoline and 2-phenylquinazoline as potential therapeutic candidates for the treatment of TSEs. From the synthesis and screening of constructed libraries we have shown that an electron-rich aromatic ring attached through an amine linker to the position para to the ring nitrogen is beneficial to both binding to PrPC and the suppression of PrPSc accumulation for acridine and 2-methylquinoline analogues. 2-Phenylquinazoline analogues appear to utilise a different mode of action by binding at a different location and/or pose. We report IC(50)s in the nanomolar range. (c) 2006 Elsevier Masson SAS. All rights reserved.
• CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODE-GENERATIVE DISEASES SUCH AS TAUOPATHIES
  申请人：Sheridan Joseph M.

  公开号：US20140031547A1

  公开（公告）日：2014-01-30

  The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1δ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
• CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES SUCH AS TAUOPATHIES
  申请人：Electrophoretics Limited

  公开号：US20160354375A1

  公开（公告）日：2016-12-08

  The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1δ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
• US7678802B2
  申请人：——

  公开号：US7678802B2

  公开（公告）日：2010-03-16
• US7713983B2
  申请人：——

  公开号：US7713983B2

  公开（公告）日：2010-05-11