| 绿卡色林衍生物的合成、体外代谢及体内活性研究 |
| |
| 引用本文： | 张灵芝,蒋敏瑞,魏萍,朱启华,龚国清,卞学国,徐云根.绿卡色林衍生物的合成、体外代谢及体内活性研究[J].高等学校化学学报,2017,38(10). |
| |
| 作者姓名： | 张灵芝 蒋敏瑞 魏萍 朱启华 龚国清 卞学国 徐云根 |
| |
| 作者单位： | 1. 中国药科大学药物化学系,南京,210009;2. 中国药科大学药理系,南京,210009;3. 南京医工医药技术有限公司,南京,210009 |
| |
| 基金项目： | 江苏省产学研前瞻性联合研究项目(批准号:BY2015072-02)资助.Supported by the Research and Production of Prospective Joint Research Project of Jiangsu Province |
| |
| 摘 要： | 将选择性5-HT2C受体激动剂类减肥药绿卡色林分子中的仲胺转化成氨基甲酸酯类前药,设计合成了13个氨基甲酸酯类化合物.新化合物的结构经核磁共振波谱、红外光谱及高分辨质谱确证.通过体外代谢稳定性实验,筛选出半衰期长且可通过代谢持续产生绿卡色林的新化合物6b.对化合物6b的大鼠减肥药理实验结果表明,在日剂量相同的条件下,化合物6b给药1次/d比绿卡色林给药2次/d的减肥效果略好.
|
| 关 键 词： | 绿卡色林 前药 代谢稳定 体内活性 |
Synthesis,Metabolic Stability and Biological Activity in vivo of Lorcaserin Derivatives |
| |
| ZHANG Lingzhi,JIANG Minrui,WEI Ping,ZHU Qihua,GONG Guoqing,BIAN Xueguo,XU Yungen.Synthesis,Metabolic Stability and Biological Activity in vivo of Lorcaserin Derivatives[J].Chemical Research In Chinese Universities,2017,38(10). |
| |
| Authors: | ZHANG Lingzhi JIANG Minrui WEI Ping ZHU Qihua GONG Guoqing BIAN Xueguo XU Yungen |
| |
| Abstract: | To improve oral bioavailability and metabolic stability while maintaining the activity and selectivity, 13 carbamate prodrugs of lorcaserin were designed and synthesized by the structural modification of the secondary amine group. The structure of target compounds were confirmed by 1 H NMR, 13 C NMR, HRMS and IR. In vitro metabolic stabilities of 13 target compounds were explored by rat liver microsomes incubation experiment, among which compound 6b showed a longer half-life and can generate lorcaserin continuously by metabolism. In high-fat diet rats model, compound 6b exhibited slightly better weight loss effect than lorcaserin at the equimolar daily doses. |
| |
| Keywords: | Lorcaserin Prodrug Metabolic stability Biological activity in vivo |
| 本文献已被 CNKI 万方数据 等数据库收录！ |
|
