2-methyl-4-(2-amino-4-methoxy)anilinoquinazoline | 1494589-74-0

• 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: 2-methyl-4-(2-amino-4-methoxy)anilinoquinazoline
• 英文别名: 4-methoxy-1-N-(2-methylquinazolin-4-yl)benzene-1,2-diamine
• CAS: 1494589-74-0
• 化学式: C₁₆H₁₆N₄O
• 分子量: 280.329
• InChiKey: SEYHXPVPFWVGKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-4-(2-amino-4-methoxy)anilinoquinazoline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 1.0h， 生成 2-methyl-4-(7-methoxy-2-oxo-3,4-dihydroquinoxalin-4(1H)-yl)quinazoline
  参考文献：
  名称：

  N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof

  摘要：

  本发明涉及公式I的化合物或其药学上可接受的盐，其制备方法，包含该化合物的药物组合物，以及其在制造用于治疗疾病或障碍的药物中的应用，其中R1、R2、R5、R6、X、Y、Q、W、n1和n2的定义如描述中所述。

  公开号：

  US20150141407A1
• 作为产物：
  描述：

  2-methyl-4-(2-nitro-4-methoxy)anilinoquinazoline 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以260 mg的产率得到2-methyl-4-(2-amino-4-methoxy)anilinoquinazoline
  参考文献：
  名称：

  N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof

  摘要：

  本发明涉及公式I的化合物或其药学上可接受的盐，其制备方法，包含该化合物的药物组合物，以及其在制造用于治疗疾病或障碍的药物中的应用，其中R1、R2、R5、R6、X、Y、Q、W、n1和n2的定义如描述中所述。

  公开号：

  US20150141407A1

文献信息

• Scaffold Hopping-Driven Optimization of 4-(Quinazolin-4-yl)-3,4-dihydroquinoxalin-2(1<i>H</i>)-ones as Novel Tubulin Inhibitors
  作者：Li Jiang、Masuo Goto、Dong-Qing Zhu、Pei-Ling Hsu、Kang-Po Li、Mutian Cui、Xiaoyang He、Susan Lynne Morris-Natschke、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1021/acsmedchemlett.9b00352

  日期：2020.1.9

  Scaffold hopping-driven lead optimizations were performed based on our prior lead 7-methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one ( 2a) by C-ring expansion and isometric replacement of the A/B-ring, successively, aimed at finding new potential alternative drug candidates with different scaffold(s), high antitumor activity, and other improved properties to replace prior, once promising drug candidates that failed in further studies. Two series of new compounds 7 (a-d) and 13 (a-j) were synthesized and evaluated for antitumor activity, leading to the discovery of three highly potent compounds 13c, 13d, and 13e with different scaffolds. They exhibited similar high antitumor activity with single digital low nanomolar GI(50) values (4.6-9.6 nM) in cellular assays, comparable to lead 2a, clinical drug candidate CA-4, and paclitaxel in the same assays. Further biological evaluations identified new active compounds as tubulin polymerization inhibitors targeting the colchicine binding site. Moreover, 13d showed better aqueous solubility than 2a and a similar log P value.
• N-ARYL UNSATURATED FUSED RING TERTIARY AMINE COMPOUND, PREPARATION METHOD THEREOF AND ANTITUMOR APPLICATION THEREOF
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：EP2857393B1

  公开（公告）日：2018-09-12
• Optimization of 4-(<i>N</i>-Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site
  作者：Xiao-Feng Wang、Fang Guan、Emika Ohkoshi、Wanjun Guo、Lili Wang、Dong-Qing Zhu、Sheng-Biao Wang、Li-Ting Wang、Ernest Hamel、Dexuan Yang、Linna Li、Keduo Qian、Susan L. Morris-Natschke、Shoujun Yuan、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1021/jm4016526

  日期：2014.2.27

  The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (la and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a-c and 5a-m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (50, the most potent compound, exhibited high in vitro cytotoxic activity (GI(50) 1.9-3.2 nM), significant potency against tubulin assembly (IC50 0.77 mu M), and substantial inhibition of colchicine binding (99% at 5 mu M). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose.
• US9751884B2
  申请人：——

  公开号：US9751884B2

  公开（公告）日：2017-09-05