芳基哌嗪苯并恶嗪类化合物的设计合成及生物活性研究-药学学报.PDFVIP

药学学报 Acta Pharmaceutica Sinica 2012, 47 (6): 755−763 ·755 · 芳基哌嗪苯并噁嗪类化合物的设计、合成及生物活性研究 1 1 1 1 2 2 1* 郑永勇 , 解 鹏 , 张 瑾 , 李建其 , 郭 琳 , 俞蕾平 , 周 斌 (1. 上海医药工业研究院, 上海 200040; 2. 中国科学院上海药物研究所, 上海 201203) 摘要: 以具有5-HT 再摄取/5-HT 1A 双重活性化合物为训练集分子, 构建药效团模型, 设计合成了 8 个未见文 献报道的芳基哌嗪苯并噁嗪类新化合物, 结构经 1H NMR 及 HR-MS 分析确证。5-HT 再摄取和 5-HT1A 受体结合 实验显示, VI1 和 VI7 为 5-HT 再摄取/5-HT 1A 双重活性化合物。VI1 和 VI7 可作为先导结构指导后续活性新化合物 的设计和合成研究。 关键词: 芳基哌嗪苯并噁嗪衍生物; 药效团模型; 5-HT 再摄取; 5-HT1A 中图分类号: R916 文献标识码: A 文章编号: 0513-4870 (2012) 06-0755-09 Design, synthesis and bioactivity of aryl piperazine benzo[b][1,4]oxazine derivatives 1 1 1 1 2 2 1* ZHENG Yong-yong , XIE Peng , ZHANG Jin , LI Jian-qi , GUO Lin , YU Lei-ping , ZHOU Bin (1. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China; 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China) Abstract : Compounds with serotonin reuptake inhibition/5-HT1A dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio® . Based on the model, 8 novel aryl piperazine benzo [b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI and VI showed potent functional 1 7 activities at both 5-HT transporter and 5-HT1A receptor, which