6,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4-amine | 1357295-04-5

• 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: 6,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4-amine
• CAS: 1357295-04-5
• 化学式: C₁₇H₁₇N₃O₃
• 分子量: 311.34
• InChiKey: ATGVSXQGABWGGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-bromo(1,7-dicarba-closo-dodecaborane(12)) 、 6,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4-amine 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium tert-butylate 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2‐Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres

  摘要：

  摘要多药耐药性是临床癌症治疗的一大挑战。特别是某些ATP结合盒（ABC）转运蛋白的过度表达，如外排转运蛋白ABCG2（又称乳腺癌耐药蛋白（BCRP）），与癌症治疗中化疗药物耐药性的产生有关，因此靶向抑制BCRP介导的转运可能会导致这种（多药）耐药性（MDR）的逆转。在之前的一项研究中，我们介绍了在聚甲氧基化的 2-苯基喹唑啉-4-胺骨架中引入硼碳簇，即闭合二碳化十二硼烷或碳硼烷，作为无机药基。在这项工作中，研究范围扩展到了相应的酰胺衍生物。由于大多数酰胺衍生物的溶解性较差，只有酰胺衍生物 QCe 和两种胺衍生物 DMQCc 和 DMQCd 得到了进一步研究。硼烷通常被认为是对立体要求较高的苯基模拟物或异构体。因此，我们还研究了最有前途的碳硼烷衍生物的有机苯基和立体要求苛刻的金刚烷基类似物。研究表明，之前描述的五甲氧基化 N-硼烷基-2-苯基喹唑啉-4-胺 DMQCd 在细胞毒性、抑制人类 ABCG2 转运体以及逆转 BCRP 介导的米托蒽醌在 MDCKII-hABCG2 和 HT29 结肠癌细胞中的抗药性方面远远优于其有机类似物。我们的研究结果表明，DMQCd是一种很有希望的候选药物，可用于进一步的体外和体内研究，以联合治疗ABCG2表达缺失的癌症。

  DOI：

  10.1002/cmdc.202300506
• 作为产物：
  描述：

  4-chloro-6,7-dimethoxy-2-(4-methoxyphenyl)quinazoline 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.05h， 生成 6,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4-amine
  参考文献：
  名称：

  Cytotoxic potential of novel 6,7-dimethoxyquinazolines

  摘要：

  Herein, we report the synthesis and cytotoxicity of a series of substituted 6,7-dimethoxyquinazoline derivatives. The cytotoxic activity of all synthesized compounds has been evaluated against HCT116p53(+/+) and HCT116p53(-/-) colon cancer cells and a HEY ovarian cancer cell line naturally resistant to cisplatin. Nine of the tested compounds showed significant cytotoxicity in all cell lines at 10 mu M. The most promising derivative (7c) showed IC(50)values of 0.7 and 1.7 mu M in the two colon cancer cell lines. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.020

文献信息

• Suzuki–Miyaura coupling of quinazolines containing an unprotected NH₂ group: Synthesis and biological testing of quinazoline derivatives
  作者：Yadagiri Pulipati、Venkateshwarlu Gurram、S. Vijaya Laxmi、Yennam Satyanarayana、Karan Singh、Vinod Kumar、Somesh Sharma、Narender Pottabathini、Vijaya Bhaskara Reddy Iska

  DOI：10.1080/00397911.2017.1315672

  日期：2017.6.18

  ABSTRACT A robust approach to 4-amino quinazoline bi-aryl compounds was developed through Suzuki–Miyaura coupling reaction of quinazoline containing an unprotected NH2 group and arylboronic acids. Pd(dcpf)Cl2 was found to be an efficient catalyst for the reaction. All the compounds were evaluated for antimicrobial activity against gram-positive and gram-negative bacteria and fungi. One of the compounds

  摘要 通过含有未保护的 NH2 基团的喹唑啉和芳基硼酸的 Suzuki-Miyaura 偶联反应，开发了 4-氨基喹唑啉双芳基化合物的稳健方法。发现 Pd(dcpf)Cl2 是该反应的有效催化剂。评估所有化合物对革兰氏阳性和革兰氏阴性细菌和真菌的抗微生物活性。发现其中一种化合物 3l 对白色念珠菌的活性高于标准咪康唑。图形概要
• Cytotoxic potential of novel 6,7-dimethoxyquinazolines
  作者：Mange R. Yadav、Fedora Grande、Bishram S. Chouhan、Prashant P. Naik、Rajani Giridhar、Antonio Garofalo、Nouri Neamati

  DOI：10.1016/j.ejmech.2011.12.020

  日期：2012.2

  Herein, we report the synthesis and cytotoxicity of a series of substituted 6,7-dimethoxyquinazoline derivatives. The cytotoxic activity of all synthesized compounds has been evaluated against HCT116p53(+/+) and HCT116p53(-/-) colon cancer cells and a HEY ovarian cancer cell line naturally resistant to cisplatin. Nine of the tested compounds showed significant cytotoxicity in all cell lines at 10 mu M. The most promising derivative (7c) showed IC(50)values of 0.7 and 1.7 mu M in the two colon cancer cell lines. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Carboranes as Potent Phenyl Mimetics: A Comparative Study on the Reversal of ABCG2‐Mediated Drug Resistance by Carboranylquinazolines and Their Organic Isosteres
  作者：Philipp Stockmann、Lydia Kuhnert、Tamara Krajnović、Sanja Mijatović、Danijela Maksimović‐Ivanić、Walther Honscha、Evamarie Hey‐Hawkins

  DOI：10.1002/cmdc.202300506

  日期：2024.1.15

  Multidrug resistance is a major challenge in clinical cancer therapy. In particular, overexpression of certain ATP‐binding cassette (ABC) transporter proteins, like the efflux transporter ABCG2, also known as breast cancer resistance protein (BCRP), has been associated with the development of resistance to applied chemotherapeutic agents in cancer therapies, and therefore targeted inhibition of BCRP‐mediated transport might lead to reversal of this (multidrug) resistance (MDR). In a previous study, we have described the introduction of a boron‐carbon cluster, namely closo‐dicarbadodecaborane or carborane, as an inorganic pharmacophore into a polymethoxylated 2‐phenylquinazolin‐4‐amine backbone. In this work, the scope was extended to the corresponding amide derivatives. As most of the amide derivatives suffered from poor solubility, only the amide derivative QCe and the two amine derivatives DMQCc and DMQCd were further investigated. Carboranes are often considered as sterically demanding phenyl mimetics or isosteres. Therefore, the organic phenyl and sterically demanding adamantyl analogues of the most promising carborane derivatives were also investigated. The studies showed that the previously described DMQCd, a penta‐methoxylated N‐carboranyl‐2‐phenylquinazolin‐4‐amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP‐mediated mitoxantrone resistance in MDCKII‐hABCG2 and HT29 colon cancer cells. Our results indicate that DMQCd is a promising candidate for further in vitro as well as in vivo studies in combination therapy for ABCG2‐overexpressing cancers.

  摘要多药耐药性是临床癌症治疗的一大挑战。特别是某些ATP结合盒（ABC）转运蛋白的过度表达，如外排转运蛋白ABCG2（又称乳腺癌耐药蛋白（BCRP）），与癌症治疗中化疗药物耐药性的产生有关，因此靶向抑制BCRP介导的转运可能会导致这种（多药）耐药性（MDR）的逆转。在之前的一项研究中，我们介绍了在聚甲氧基化的 2-苯基喹唑啉-4-胺骨架中引入硼碳簇，即闭合二碳化十二硼烷或碳硼烷，作为无机药基。在这项工作中，研究范围扩展到了相应的酰胺衍生物。由于大多数酰胺衍生物的溶解性较差，只有酰胺衍生物 QCe 和两种胺衍生物 DMQCc 和 DMQCd 得到了进一步研究。硼烷通常被认为是对立体要求较高的苯基模拟物或异构体。因此，我们还研究了最有前途的碳硼烷衍生物的有机苯基和立体要求苛刻的金刚烷基类似物。研究表明，之前描述的五甲氧基化 N-硼烷基-2-苯基喹唑啉-4-胺 DMQCd 在细胞毒性、抑制人类 ABCG2 转运体以及逆转 BCRP 介导的米托蒽醌在 MDCKII-hABCG2 和 HT29 结肠癌细胞中的抗药性方面远远优于其有机类似物。我们的研究结果表明，DMQCd是一种很有希望的候选药物，可用于进一步的体外和体内研究，以联合治疗ABCG2表达缺失的癌症。