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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:884  下载量:193
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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