7-烷氧基-6-甲氧基-4-取代苯胺基-1,2,3-苯并三嗪类化合物的合成及抑制MVEC细胞增殖活性  

Synthesis and antiproliferative activity of 7-alkoxy-6-methoxy-4-substituted anilino-1,2,3-benzotriazines derivatives in MVEC cells

作　　者：栾升霖 闻家辰[1] 赵兴旺[1] 刘丹[1] 赵临襄[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2014年第4期286-292,共7页Chinese Journal of Medicinal Chemistry

基　　金：国家基础科学人才培养基金资助项目(J1103606)

摘　　要：目的设计、合成7-烷氧基-6-甲氧基-4-取代苯胺基-1,2,3-苯并三嗪类化合物,并测定其体外抗增殖活性。方法以4-羟基-3-甲氧基苯腈为原料,与不同卤代烷成醚,再经硝化、硝基还原制得4-烷氧基-2-氨基-5-甲氧基苯腈中间体;中间体与不同取代的苯胺发生重氮化-偶合反应后再经环合、Dimroth重排反应得到目标化合物。采用MTT法,以瓦他拉尼(vatalanib)为阳性对照药,测试目标化合物对大鼠脑微血管内皮细胞(MVEC)的抗增殖活性。结果与结论合成了15个新化合物,经IR、MS、1H-NMR确证结构;初步药理实验结果显示,多个目标化合物具有明显的抗MVEC增殖活性。其中7f、7i、7j、7l、7o的活性强于阳性对照,其GI50分别为15.50、22.66、17.35、16.85、14.77μmol·L-1。Based on the previous research about 4-substituted anilino-1,2,3-benzotriazines, a series of novel 7-alkoxy-6-methoxy-4-substituted anilino-1,2,3-benzotriazines were designed and synthesized to expose more potent anticancer drugs and fulfill structure-activity relationship. 15 Target compounds were synthesized and identified by IR, MS and t H-NMR spectra. The antiproliferative effects against murine microvascular en- dothelial cells（MVEC） of these compounds were tested using the M＇I-T assay with vatalanib as a positive control. Compounds 7f,7i,7j ,71 and 70 show more potent activity than vatalanib with GIs0 values 15.50, 22.66,17.35,16. 85 and 14.77 ixmol＂ L - l respectively. Preliminary structure-activity relationship was con- cluded from this research.

关 键 词：1 2 3-苯并三嗪 抗增殖活性 构效关系 

分 类 号：R914.4[医药卫生—药物化学]