2-(3,4-dimethoxyphenyl)-N-(4-nitrophenyl)quinazolin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(3,4-dimethoxyphenyl)-N-(4-nitrophenyl)quinazolin-4-amine
• 化学式: C₂₂H₁₈N₄O₄
• 分子量: 402.409
• InChiKey: IEQRCWORKDNNAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-N-(4-nitrophenyl)quinazolin-4-amine 在 铁粉 、 calcium chloride 作用下， 以 乙醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modelling insights of 2-arylquinazoline benzamide derivatives as anti-tubercular agents

  摘要：

  DOI：

  10.1016/j.molstruc.2020.128493
• 作为产物：
  描述：

  2-(3,4-dimethoxyphenyl)quinazolin-4(3H)-one 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 生成 2-(3,4-dimethoxyphenyl)-N-(4-nitrophenyl)quinazolin-4-amine
  参考文献：
  名称：

  2,4-取代的喹唑啉类化合物作为乳腺癌抗性蛋白（ABCG2）的高效抑制剂的合成与生物学研究

  摘要：

  ABC转运蛋白超家族成员ABCG2的表达与多种癌症的临床结局相关，并且通常与化疗中多药耐药性（MDR）的发生有关。用有效的和选择性的抑制剂抑制转运蛋白可能是更有效地治疗癌症并改善癌症患者治疗的一种方法。 最近，我们报道了基于喹唑啉支架的新抑制剂的合成。在本研究中，探索了更多的结构变异。具有3,4-二甲氧基和间位或对位的化合物发现硝基取代基是ABCG2的高效抑制剂。最有效的化合物比AB143最好的抑制剂之一Ko143的效力高出五倍。为了确定新化合物对ABCG2的选择性，还研究了它们对ABCB1和ABCC1的抑制作用，从而鉴定了选择性抑制剂和广谱抑制剂。此外，探索了内在的细胞毒性和功效，涉及逆转对SN-38和米托蒽醌的多药耐药性。最有效的化合物能够逆转EC 50对细胞抑制剂的耐药性低于20 nM的值。另外，研究了抑制剂与ABCG2底物Hoechst 33342之间的相互作用类型，产生竞争性和非

  DOI：

  10.1016/j.ejmech.2017.08.020

文献信息

• Synthesis and biological investigation of 2,4-substituted quinazolines as highly potent inhibitors of breast cancer resistance protein (ABCG2)
  作者：Michael K. Krapf、Jennifer Gallus、Michael Wiese

  DOI：10.1016/j.ejmech.2017.08.020

  日期：2017.10

  chemotherapy. Inhibition of the transport protein by potent and selective inhibitors might be a way to treat cancer more efficiently and improve the therapy of cancer patients. Recently we reported the synthesis of new inhibitors based on a quinazoline scaffold. In the present study more structural variations were explored. Compounds with 3,4-dimethoxy groups and meta or para nitro substituents were found

  ABC转运蛋白超家族成员ABCG2的表达与多种癌症的临床结局相关，并且通常与化疗中多药耐药性（MDR）的发生有关。用有效的和选择性的抑制剂抑制转运蛋白可能是更有效地治疗癌症并改善癌症患者治疗的一种方法。 最近，我们报道了基于喹唑啉支架的新抑制剂的合成。在本研究中，探索了更多的结构变异。具有3,4-二甲氧基和间位或对位的化合物发现硝基取代基是ABCG2的高效抑制剂。最有效的化合物比AB143最好的抑制剂之一Ko143的效力高出五倍。为了确定新化合物对ABCG2的选择性，还研究了它们对ABCB1和ABCC1的抑制作用，从而鉴定了选择性抑制剂和广谱抑制剂。此外，探索了内在的细胞毒性和功效，涉及逆转对SN-38和米托蒽醌的多药耐药性。最有效的化合物能够逆转EC 50对细胞抑制剂的耐药性低于20 nM的值。另外，研究了抑制剂与ABCG2底物Hoechst 33342之间的相互作用类型，产生竞争性和非
• Investigation of quinazolines as inhibitors of breast cancer resistance protein (ABCG2)
  作者：Kapil Juvale、Jennifer Gallus、Michael Wiese

  DOI：10.1016/j.bmc.2013.10.007

  日期：2013.12

  Chemotherapy is one of the major forms of cancer treatment. Unfortunately, tumors are prone to multidrug resistance leading to failure of treatment. Breast cancer resistance protein (BCRP), the second member of ABC transporter subfamily G, has been found to play a major role in drug efflux and hence multidrug resistance. Until now, very few potent and selective BCRP inhibitors like Ko143 have been identified. In the search for more potent and selective BCRP inhibitors, we synthesized and investigated a series of differently substituted quinazoline compounds. Several variations at positions 2, 4, 6 and 7 of the quinazoline scaffold were carried out to develop a structure-activity-relationship analysis for these compounds. It was found that compounds bearing a phenyl substituent at position 2 of the 4-anilinoquinazoline scaffold were most potent. On the aniline ring at position 4 of the quinazoline moiety substituents like NO2, CN, CF3 led to very high BCRP inhibition potencies. The most potent compounds were further investigated for their intrinsic cytotoxicity and their ability to reverse the multidrug resistance. Compound 20, an anilinoquinazoline bearing a phenyl ring at position 2 and meta-nitro substitution on the 4-anilino ring, was found to have the highest therapeutic ratio. The most active compounds from each variation were also investigated for their effect on BCRP expression. It was found that compound 20 has no significant effect on BCRP expression, while compound 31 decreased the surface BCRP expression. The only difference in the two compounds was the presence of a 3,4-dimethoxyphenyl ring in compound 31 instead of phenyl substitution at position 2 of the quinazoline moiety. From the study of all target compounds, compound 20 was the most prominent compound having inhibitory potency even higher than Ko143, the most potent BCRP inhibitor known. Compound 20 was also found to be selective towards BCRP with a very high therapeutic ratio. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis, biological evaluation and molecular modelling insights of 2-arylquinazoline benzamide derivatives as anti-tubercular agents
  作者：Satyaveni Malasala、Md Naiyaz Ahmad、Jitendra Gour、Manjulika Shukla、Grace Kaul、Abdul Akhir、Srikanth Gatadi、Y.V. Madhavi、Sidharth Chopra、Srinivas Nanduri

  DOI：10.1016/j.molstruc.2020.128493

  日期：2020.10