4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepinyl))-2-methylquinazoline | 1415261-97-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepinyl))-2-methylquinazoline
• 英文别名: N²-[4-(2-methyl)quinazolinyl]-7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepine；7-Methoxy-2-(2-methylquinazolin-4-yl)-1,3,4,5-tetrahydro-2-benzazepine；7-methoxy-2-(2-methylquinazolin-4-yl)-1,3,4,5-tetrahydro-2-benzazepine
• CAS: 1415261-97-0
• 化学式: C₂₀H₂₁N₃O
• 分子量: 319.406
• InChiKey: WDUAZKXUYRIVTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-甲氧基-2,3,4,5-四氢-1H-2-苯并氮杂卓-1-酮 在 lithium aluminium tetrahydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 18.0h， 生成 4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepinyl))-2-methylquinazoline
  参考文献：
  名称：

  Optimization of 4-(N-Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site

  摘要：

  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.

  DOI：

  10.1021/jm4016526

文献信息

• N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：US20150141407A1

  公开（公告）日：2015-05-21

  The present invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, its preparation method, a pharmaceutical composition comprising the compound, and its use in manufacture of a medicament for treatment of a disease or disorder, wherein R 1 , R 2 , R 5 , R 6 , X, Y, Q, W, n 1 and n 2 are defined as those stated in the description.

  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。
• 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
• US9751884B2
  申请人：——

  公开号：US9751884B2

  公开（公告）日：2017-09-05
• 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.