N-(3-bromophenyl)-7-methoxy-6-nitroquinazoline-4-amine | 171745-10-1

• 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-bromophenyl)-7-methoxy-6-nitroquinazoline-4-amine
• 英文别名: N-(3-bromophenyl)-7-methoxy-6-nitroquinazolin-4-amine
• CAS: 171745-10-1
• 化学式: C₁₅H₁₁BrN₄O₃
• 分子量: 375.181
• InChiKey: CZBTZBBBQGIOGA-UHFFFAOYSA-N

物化性质

• 沸点：
  533.5±50.0 °C(Predicted)
• 密度：
  1.645±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-bromophenyl)-7-methoxy-6-nitroquinazoline-4-amine 在 sodium tetrahydroborate 、 草酰氯 、 nickel(II) chloride hexahydrate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.92h， 生成 (R)-N-(4-((3-bromophenyl)amino)-7-methoxyquinazolin-6-yl)-2-oxooxazolidine-4-carboxamide
  参考文献：
  名称：

  6-Oxooxazolidine–quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR

  摘要：

  Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFR(T790M) and EGFR(L858R) kinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2016.04.046
• 作为产物：
  描述：

  7-甲氧基-6-硝基喹唑啉-4(3H)-酮 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 N-(3-bromophenyl)-7-methoxy-6-nitroquinazoline-4-amine
  参考文献：
  名称：

  Design of balanced dual-target inhibitors of EGFR and microtubule

  摘要：

  DOI：

  10.1016/j.bioorg.2023.107087

文献信息

• QUINAZOLINE DERIVATIVE AND PREPARATION METHOD THEREFOR
  申请人：CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD.

  公开号：US20160214964A1

  公开（公告）日：2016-07-28

  The present invention relates to a quinazoline derivative shown in formula (I) and a preparation method therefor, a pharmaceutical composition comprising the compound shown in formula (I), and an application of the compound in preparing drugs for curing and preventing tumors. The compound of the present invention can irreversibly prevent EGFR phosphorylation, and effectively depress signal transduction of cancer cells, and accordingly has higher anti-tumor activity in vitro and in vivo,

  本发明涉及一种在式（I）中显示的喹唑啉衍生物及其制备方法，包括式（I）中显示的化合物的药物组合物，以及该化合物在制备治疗和预防肿瘤的药物中的应用。本发明的化合物可以不可逆地阻止EGFR磷酸化，有效抑制癌细胞的信号转导，因此在体外和体内具有更高的抗肿瘤活性。
• Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor
  作者：Alexander J. Bridges、Hairong Zhou、Donna R. Cody、Gordon W. Rewcastle、Amy McMichael、H. D. Hollis Showalter、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm9503613

  日期：1996.1.1

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF CANCER
  申请人：Chia Tai Tianqing Pharmaceutical Group Co.,Ltd

  公开号：EP3050880B1

  公开（公告）日：2019-06-19
• US9725439B2
  申请人：——

  公开号：US9725439B2

  公开（公告）日：2017-08-08
• 6-Oxooxazolidine–quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR
  作者：Jiaan Shao、En Chen、Ke Shu、Wenteng Chen、Guolin Zhang、Yongping Yu

  DOI：10.1016/j.bmc.2016.04.046

  日期：2016.8

  Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFR(T790M) and EGFR(L858R) kinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants. (C) 2016 Published by Elsevier Ltd.