N-(3-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: N-(3-nitrophenyl)quinazolin-4-amine
• 英文别名: (3-nitro-phenyI)-quinazolin-4-yl-amine；(3-nitro-phenyl)-quinazolin-4-yl-amine；4-(3-nitroanilino)quinazoline；Cambridge id 6371352
• 化学式: C₁₄H₁₀N₄O₂
• 分子量: 266.259
• InChiKey: XJOHOCFXDMKHIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-羟基喹唑啉 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 9.0h， 生成 N-(3-nitrophenyl)quinazolin-4-amine
  参考文献：
  名称：

  Investigation of quinazolines as inhibitors of breast cancer resistance protein (ABCG2)

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.10.007

文献信息

• Facile and efficient synthesis and biological evaluation of 4-anilinoquinazoline derivatives as EGFR inhibitors
  作者：Zheng Wang、Xue Wu、Li Wang、Jiao Zhang、Jianli Liu、Zhongxing Song、Zhishu Tang

  DOI：10.1016/j.bmcl.2016.04.032

  日期：2016.6

  Series of 4-anilinoquinazoline derivatives were conveniently and efficiently synthesized and their antitumor activities were evaluated by MTT assay in three human cancer cell lines: H1975, HepG2 and SMMC-7721. New compounds 19a-19h were designed and synthesized to seek for powerful EGFR inhibitors and to explore whether methyl group at C-2 position of quinazoline ring has a positive effect on EGFR

  方便，有效地合成了一系列4-苯胺基喹唑啉衍生物，并通过MTT分析在三种人类癌细胞系H1975，HepG2和SMMC-7721中评估了它们的抗肿瘤活性。设计并合成了新的化合物19a-19h，以寻找功能强大的EGFR抑制剂，并探索喹唑啉环C-2位处的甲基是否对EGFR抑制具有积极作用。发现19a-19h的所有化合物对所有三种细胞系均有效，并且发现5种化合物（19c，19d和19f-19h）对H1975的毒性高于吉非替尼。SAR研究表明，喹唑啉环C-2位的甲基可以显着提高4-苯胺基喹唑啉的抗肿瘤能力。根据蛋白质印迹分析的结果也得出了相同的结论。在所有测试的化合物中，19g对H1975表现出极强的效力，IC50值为0.11μM，明显低于吉非替尼（1.23μM）。Western印迹分析的结果表明，化合物19c和19g可以显着抑制磷酸化EGFR的表达，尤其是19g几乎完全被抑制。
• Therapeutic preparations containing quinazoline derivatives
  申请人：ZENECA LIMITED

  公开号：EP0520722B1

  公开（公告）日：1996-12-27
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF HERPESVIRAL INFECTIONS
  申请人：GPC Biotech AG

  公开号：EP1673346A1

  公开（公告）日：2006-06-28
• Quinazoline derivatives for the treatment of herpesviral infections
  申请人：Herget Thomas

  公开号：US20070123537A1

  公开（公告）日：2007-05-31

  The present invention relates to phenyl-quinazolinyl-amine derivatives and pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one of these derivatives and/or pharmaceutically salts thereof, as well as the use of these derivatives for the prophylaxis and/or treatment of herpesviral induced infections, including opportunistic infections, especially for the prophylaxis and/or treatment of infections and diseases induced by HCMV.
• [EN] QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF HERPESVIRAL INFECTIONS<br/>[FR] DERIVES DE QUINAZOLINE POUR LE TRAITEMENT D'INFECTIONS VIRALES HERPETIQUES
  申请人：AXXIMA PHARMACEUTICALS AG

  公开号：WO2005040125A1

  公开（公告）日：2005-05-06

  The present invention relates to phenyl-quinazolinyl-amine derivatives and pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one of these derivatives and/or pharmaceutically salts thereof, as well as the use of these derivatives for the prophylaxis and/or treatment of herpesviral induced infections, including opportunistic infections, especially for the prophylaxis and/or treatment of infections and diseases induced by HCMV.