N-(3,4-dimethoxyphenyl)-2-phenylquinazolin-4-amine | 1401688-28-5

• 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-(3,4-dimethoxyphenyl)-2-phenylquinazolin-4-amine
• CAS: 1401688-28-5
• 化学式: C₂₂H₁₉N₃O₂
• 分子量: 357.412
• InChiKey: LUUUIUBMYQYODQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 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：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 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 8.0h， 生成 N-(3,4-dimethoxyphenyl)-2-phenylquinazolin-4-amine
  参考文献：
  名称：

  4-Substituted-2-phenylquinazolines as inhibitors of BCRP

  摘要：

  We investigated several 2-phenylquinazolines with different substitutions at position 4 for their BCRP inhibition. Compounds with phenyl ring attached via an amine-containing linker at position 4 were found to be potent inhibitors of BCRP. In general compounds with meta substitution of phenyl ring at position 4 were found to have higher inhibitory effect, compound 12 being the most potent and selective towards BCRP. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.024

文献信息

• Synthesis and Biological Evaluation of 4-Anilino-quinazolines and -quinolines as Inhibitors of Breast Cancer Resistance Protein (ABCG2)
  作者：Michael K. Krapf、Michael Wiese

  DOI：10.1021/acs.jmedchem.6b00330

  日期：2016.6.9

  of cancer often fails due to overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCG2, triggering active efflux of various structurally unrelated drugs. This so-called multidrug resistance (MDR) may be reversed by selective, potent, and nontoxic inhibitors of ABCG2. As only a few potent inhibitors are known, new compounds based on a 4-substituted-2-phenylquinazoline scaffold

  癌症的化学疗法治疗通常会因ATP结合盒（ABC）转运蛋白（如ABCG2）的过表达而失败，从而触发各种结构上不相关的药物的主动流出。这种所谓的多药耐药性（MDR）可以通过ABCG2的选择性，有效和无毒抑制剂来逆转。因为仅已知几种有效的抑制剂，所以研究了基于4-取代的-2-苯基喹唑啉骨架的新化合物。用羟基，氰基，硝基，乙酰胺基和氟取代可导致对ABCG2的高度抑制活性。在MTT功效测定中证实了逆转最具活性的化合物的MDR的能力。此外，发现可忽略的低固有细胞毒性导致高治疗率。对于喹唑啉化合物，对ABCB1和ABCC1的抑制活性的研究产生了对ABCG2的高选择性。基于喹啉的类似物显示较低的抑制活性和选择性。该研究产生了各种有希望的化合物，其中一些具有比标准抑制剂Ko143更好的性能。
• FEATURE QUANTITY CALCULATING METHOD, FEATURE QUANTITY CALCULATING PROGRAM AND FEATURE QUANTITY CALCULATING DEVICE, SCREENING METHOD, SCREENING PROGRAM AND SCREENING DEVICE, COMPOUND CREATING METHOD, COMPOUND CREATING PROGRAM AND COMPOUND CREATING DEVICE
  申请人：FUJIFILM Corporation

  公开号：EP3951785A1

  公开（公告）日：2022-02-09

  Provided are a feature quantity calculating method, a feature quantity calculating program, and a feature quantity calculating device which enable calculation of a feature quantity accurately showing chemical properties of a target structure, a screening method, a screening program, and a screening device which enable efficient screening of a pharmaceutical candidate compound using a feature quantity, and a compound creating method, a compound creating program, and a compound creating device which enable efficient creation of a three-dimensional structure of a pharmaceutical candidate compound using a feature quantity. Since the chemical properties of target structures are exhibited as the result of an interaction between the target structure and probes in the periphery thereof, the fact that the degree of accumulation of the probes is similar between target structures indicates that the chemical properties of the target structures are similar. Therefore, the feature quantity accurately showing the chemical properties of the target structure can be calculated using the feature quantity calculating method according to one aspect of the present invention.

  本发明提供了一种特征量计算方法、特征量计算程序和特征量计算装置，可计算出精确显示目标结构化学特性的特征量；一种筛选方法、筛选程序和筛选装置，可利用特征量高效筛选候选药物化合物；以及一种化合物创建方法、化合物创建程序和化合物创建装置，可利用特征量高效创建候选药物化合物的三维结构。由于目标结构的化学性质是目标结构与其外围探针相互作用的结果，因此目标结构之间探针的聚集程度相似这一事实表明目标结构的化学性质相似。因此，根据本发明的一个方面，可以使用特征量计算方法计算出准确显示目标结构化学特性的特征量。
• 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.
• 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.
• FEATURE QUANTITY CALCULATING METHOD, FEATURE QUANTITY CALCULATING PROGRAM, FEATURE QUANTITY CALCULATING DEVICE, SCREENING METHOD, SCREENING PROGRAM, AND COMPOUND CREATING METHOD
  申请人：FUJIFILM Corporation

  公开号：US20220028499A1

  公开（公告）日：2022-01-27

  An object of the present invention is to provide a method, a program, and a device which enable calculation of a feature quantity accurately indicating chemical properties of a target structure. Further, another object of the present invention is to provide a method and a program which enable efficient screening of a pharmaceutical candidate compound using a feature quantity. Further, still another object of the present invention is to provide a method which enables efficient creation of a three-dimensional structure of a pharmaceutical candidate compound using a feature quantity. In a case where target structures have a similarity in the degree of accumulation of probes, this indicates that the target structures have similar chemical properties. That is, target structures having similar feature quantities calculated according to the first aspect exhibit similar chemical properties. Therefore, according to the first aspect, the feature quantity accurately showing the chemical properties of a target structure can be calculated.