2-chloro-4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]-azepinyl))quinazoline | 1415261-98-1

• 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: 2-chloro-4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]-azepinyl))quinazoline
• 英文别名: 2-(2-Chloroquinazolin-4-yl)-7-methoxy-1,3,4,5-tetrahydro-2-benzazepine；2-(2-chloroquinazolin-4-yl)-7-methoxy-1,3,4,5-tetrahydro-2-benzazepine
• CAS: 1415261-98-1
• 化学式: C₁₉H₁₈ClN₃O
• 分子量: 339.824
• InChiKey: BFSUSXCTAGEOAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 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 2-chloro-4-(N-(7-methoxy-2,3,4,5-tetrahydro-1H-benzo[c]-azepinyl))quinazoline
  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