3-((6-nitro-2-phenylquinazolin-4-yl)amino)benzoic Acid

• 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: 3-((6-nitro-2-phenylquinazolin-4-yl)amino)benzoic Acid
• 英文别名: 3-[(6-Nitro-2-phenylquinazolin-4-yl)amino]benzoic acid；3-[(6-nitro-2-phenylquinazolin-4-yl)amino]benzoic acid
• 化学式: C₂₁H₁₄N₄O₄
• 分子量: 386.367
• InChiKey: ZKSJEHRCJFEYKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-5-硝基苯甲酸 在 三光气 、 碘 、 potassium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 3.5h， 生成 3-((6-nitro-2-phenylquinazolin-4-yl)amino)benzoic Acid
  参考文献：
  名称：

  2,4,6-Substituted Quinazolines with Extraordinary Inhibitory Potency toward ABCG2

  摘要：

  Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent inhibitors of ABCG2. In this study, we identified novel inhibitors containing a 2,4,6-substituted quinazoline scaffold. Introduction of a 6-nitro function led to extraordinarily potent compounds that were highly selective for ABCG2 and also able to reverse the MDR toward the chemotherapeutic drugs SN-38 and mitoxantrone. The binding of substrate Hoechst 33342 and the two potent inhibitors 31 and 41 which differ in their mechanism of inhibition was rationalized using the recently published cryo-EM structures of ABCG2. For a better understanding of the interaction between the inhibitors and ABCG2, additional investigations regarding the ATPase activity, the interaction with Hoechst 33342, and with the conformational sensitive 5D3 antibody were carried out.

  DOI：

  10.1021/acs.jmedchem.8b01011

文献信息

• 2,4,6-Substituted Quinazolines with Extraordinary Inhibitory Potency toward ABCG2
  作者：Michael K. Krapf、Jennifer Gallus、Vigneshwaran Namasivayam、Michael Wiese

  DOI：10.1021/acs.jmedchem.8b01011

  日期：2018.9.13

  Several members of the ABC transporter superfamily play a decisive role in the development of multidrug resistance (MDR) in cancer. One of these MDR associated efflux transporters is ABCG2. One way to overcome this MDR is the coadministration of potent inhibitors of ABCG2. In this study, we identified novel inhibitors containing a 2,4,6-substituted quinazoline scaffold. Introduction of a 6-nitro function led to extraordinarily potent compounds that were highly selective for ABCG2 and also able to reverse the MDR toward the chemotherapeutic drugs SN-38 and mitoxantrone. The binding of substrate Hoechst 33342 and the two potent inhibitors 31 and 41 which differ in their mechanism of inhibition was rationalized using the recently published cryo-EM structures of ABCG2. For a better understanding of the interaction between the inhibitors and ABCG2, additional investigations regarding the ATPase activity, the interaction with Hoechst 33342, and with the conformational sensitive 5D3 antibody were carried out.