新型代谢综合征治疗药物的设计、合成及生物活性评价

发布时间：2018-09-19 15:49

【摘要】：目的设计合成新型代谢综合征治疗药物。方法以具有降脂活性的阿昔莫司做为基本结构单元,与贝特类药物的"苯氧脂酸类"药效团有机结合,设计了一类新型的苯氧脂肪酸酯类化合物,以对羟基苯胺、对羟基苄胺以及对羟基苯乙胺为原料,首先将氨基保护,然后与相应的卤代脂肪链羧酸酯成醚,然后脱除Boc保护基得到相应的胺类中间体,最后与阿昔莫司成酰胺得目标化合物,并考察了目标化合物对Triton WR-1339所致急性高脂血症小鼠血清甘油三酯和总胆固醇的影响。结果和结论合成目标化合物5个,均经~1H NMR和ESI-MS确证结构正确。初步活性评价结果表明,所合成化合物均具有一定的降脂活性,其中化合物4c的调脂活性与阳性对照苯扎贝特接近,对于新型代谢综合征药物的发现具有积极意义。
[Abstract]:Objective to design a new synthetic drug for metabolic syndrome. Methods A new class of phenoxy fatty acid esters was designed by using acymomus with lipid-lowering activity as the basic structure unit, and combined with the phenoxyllipoxylic acid group of the Bette drugs, and then the phenoxy fatty acid esters were used as p-hydroxyaniline. P-hydroxybenzylamine and p-hydroxyphenylethylamine were used as raw materials to protect the amino group, then to form an ether with the corresponding halogenated fatty chain carboxylic acid ester, and then to remove the Boc protection group to obtain the corresponding amine intermediate. The effects of the target compounds on serum triglyceride and total cholesterol in acute hyperlipidemic mice induced by Triton WR-1339 were investigated. Results and conclusion the structures of the five target compounds were confirmed by 1H NMR and ESI-MS. The results of preliminary activity evaluation showed that all the synthesized compounds had certain lipid-lowering activities, and the lipid-regulating activity of compound 4c was close to that of the positive control, which was of positive significance to the discovery of new drugs for metabolic syndrome.
【作者单位】：军事医学科学院毒物药物研究所;火箭军总医院药学部;
【基金】：国家“重大新药创制”科技重大专项基金资助项目(2012ZX09301003-001-004)
【分类号】：R914;R96

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