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吡唑-3-甲酸酯类衍生物的设计合成及体外胆固醇酯转运蛋白抑制活性研究
发表时间：2018-03-15 浏览量：1360 下载量：369
| 全部作者： | 汪鑫冉，刘春池，郝丽娟，罗昌群，赵冬梅，程卯生 |
| 作者单位： | 沈阳药科大学制药工程学院 |
| 摘 要： | 动脉粥样硬化是心血管疾病的主要病理基础。抑制胆固醇酯转运蛋白（cholesteryl ester transfer protein，CETP）的活性能够有效提高高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平、降低低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）水平，并可改善动脉粥样硬化病理过程。以Merk公司开发的Anacetrapib为先导化合物，采用母核替换策略结合药效团模型设计了吡唑-3-甲酸酯类化合物。以取代的苯乙酮为原料，经过缩合、环化等反应制备得到14个吡唑-3-甲酸酯类衍生物。采用荧光测试法测定目标化合物体外CETP抑制活性，药理结果表明化合物W-12、W-13具有较好的CETP抑制活性，有进一步研究的价值。 |
| 关 键 词： | 药物化学；胆固醇酯转运蛋白；合成；吡唑-3-甲酸酯 |
| Title： | Design, synthesis and in vitro CETP inhibitory activity evaluation of pyrazole-3-carboxylate derivatives |
| Author： | WANG Xinran, LIU Chunchi, HAO Lijuan, LUO Changqun, ZHAO Dongmei, CHENG Maosheng |
| Organization： | School of Pharmaceutical Engineering, Shenyang Pharmaceutical University |
| Abstract： | Atherosclerosis is the main basic pathology of cardiovascular disease. Inhibition of cholesteryl ester transfer protein (CETP) could increase high density lipoprotein cholesterol (HDL-C) level and decrease low density lipoprotein cholesterol (LDL-C) level, which could reduce the pathological progression of atherosclerosis. Anacetrapib developed by Merk was used as leading compound, a series of pyrazole-3-carboxylate derivatives were designed based on core replacement strategy and pharmacophore model. 14 pyrazole-3-carboxylate derivatives were prepared based on substituted acetophenone via condensation and cyclization, et al. In vitro CETP inhibitory activities of pyrazole-3-carboxylate derivatives were evaluated by fluorescence assay. The pharmacological results showed that compounds W-12 and W-13 exhibited preferable CETP inhibitory activity and had further research value. |
| Key words： | medicinal chemistry; cholesteryl ester transfer protein; synthesis; pyrazole-3-carboxylate |
| 发表期数： | 2018年3月第5期 |
| 引用格式： | 汪鑫冉，刘春池，郝丽娟，等. 吡唑-3-甲酸酯类衍生物的设计合成及体外胆固醇酯转运蛋白抑制活性研究[J]. 中国科技论文在线精品论文，2018，11（5）：490-498. |
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