贝特类调血脂药物的研究进展
The New Idea in the Synthesis of Lipid-Regulator Fibrates
DOI: 10.12677/HJMCe.2014.24007, PDF, HTML, 下载: 2,947  浏览: 11,413 
作者: 夏 莹, 额尔敦, 乌 恩:内蒙古医科大学药学院,呼和浩特
关键词: 高血脂贝特类合成进展活性评价Hyperlipidemia Fibrates Synthesis Progress Activity Evaluation
摘要: 贝特类药物在调血脂领域具有举足轻重的位置,它在降低甘油三酯,高密度脂蛋白,总胆固醇方面具有显著疗效,与临床上应用较多的他汀类药物相比,贝特类药物的不良反应较轻。本综述在对高脂血症和调血脂药物进行介绍的基础上,主要阐述了贝特类调血脂药物的作用机制,说明其优势,对近5年国内外贝特类药物的合成方向及药理活性进行综述,包括全合成的路线优化,结构改造制备双受体激动剂,改善油水分配系数,贝特类药物与具有调血脂活性的天然产物结合等,以期为贝特类的进一步研究提供方向。
Abstract: The lipid-regulating agent fibrate plays an important role in lowering the blood lipid. It can signif-icantly reduce the level of total cholesterol, triglyceride and high-density lipoprotein in blood, and it has less side-effect than the mostly used Statins. In this review, we mainly show the mechanism and advantages of the fibrates, as well as the introduction of the disease high-blood-lipid or the li-pid-regulating agents. We summary the synthesis and pharmacological activities in the past 5 years at home and abroad, including the better routes of its synthesis, changing the construction to get the double-receptor agonist, improving the oil-water partition coefficient and the binding rate in vivo. So we can get the new idea for the further study.
文章引用:夏莹, 额尔敦, 乌恩. 贝特类调血脂药物的研究进展[J]. 药物化学, 2014, 2(4): 47-53. http://dx.doi.org/10.12677/HJMCe.2014.24007

参考文献

[1] 黄焕莉, 黄守坚 (2010) 调血脂药的合理应用. 新医学, 10, 687-690.
[2] 孙吉叶, 蔡旭东等 (2012) 治疗高脂血症的新药研究进展. 现代药物与临床, 5, 435-441.
[3] 宁娜, 韩建军 (2013) 中药降血脂活性成分研究进展. 亚太传统医药, 2, 76-80.
[4] 叶希韵, 徐敏华, 李晓峰等 (2009) 山楂叶总黄酮降血脂防治鹌鹑脂肪肝形成的实验研究. 复旦学报(医学版), 2, 142-148.
[5] Son, I.S. and Kim, J.H. (2007)•Antioxidative and hypolipidemic effects of diosgenin, a steroidal of yam (Dioscorea spp.), on high-cholesterol fed rats. Bioscience, Biotechnology, and Biochemistry, 71, 3063-3071.
[6] 龚海荣, 李向平, 梁思宇 (2011) 贝特类调脂药物研究进展. 中南药学, 7, 539-542.
[7] Kiyanagi, T., Miyazaki, T., Kume, A., et al. (2006) Decrease in CETP activity by fenofibrate may increase LDL particle size measuredby HPLC method in patients with coronary artery disease. Atherosclerosis, 3, 559.
[8] Rizzo, M. and Berneis, K. (2007) The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates. Current Medical Research and Opinion, 23, 1103-1111.
[9] 郭丹杰, 徐成斌 (2008) 贝特类调脂药物在降脂领域的地位及认识. 临床药物治疗杂志, 2, l-3.
[10] van Bilsen, M. and van Nieuwenhoven, F.A. (2010) PPARs as therapeutic targets in cardiovascular disease. Expert Opinion on Therapeutic Targets, 14, 1029-1045.
[11] Undas, A. and Celińiska-Löwenhoff, M. (2007) Antiplatelet effects of micronized feno-fibrate in subjects with dyslipidemia. Polskie Archiwum Medycyny Wewnętrznej, 117, 235-240.
[12] Jeanpierre, E., Le Tourneau, T., Zawadzki, C., Van Belle, E., Mouquet, F., Susen, S., et al. (2009) Beneficial effects of fenofibrate on plaque thrombogenicity and plaque stability in atherosclerotic rabbits. Cardiovascular Pathology, 18, 140-147.
[13] Tenenbaum, A., Fisman, E.Z., Boyko, V., Benderly, M., Tanne, D., Haim, M., et al. (2006) Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. JAMA Internal Medicine, 166, 737-741.
[14] 吴洁, 固旭, 李东, 丁爱忠, 戴晓阳 (2010) 降脂药苯扎贝特合成工艺改进. 中国新药杂志, 4, 311-312.
[15] Peter, B. (1983) Process for the preparation of α-[4-(4-chlorobenzoylamin-oethyl)-phenoxy]-isobutyric acid. US Patent: 4370495.
[16] BOEHRINGER MANNHEIM GMBH (1973) Phenoxyalkylcarbonsaured-erivate and verfahrenzur herstellung der- selben. DE, 2149070.
[17] Sashidhara, K.V., Palnati, G.R., Dodda, R.P., Sonkar, R., Khanna, A.K. and Bhatia, G. (2012) Discovery of amide based fibrates as possible antidyslipidemic and antioxidant agents. European Journal of Medicinal Chemistry, 57, 302- 310.
[18] Sashidhara, K.V., Kumar, M., Sonkar, R., Singh, B.S., Khanna, A.K. and Bhatia, G. (2012) Indole-based fibrates as potential hypolipidemic and antiobesity agents. Journal of Medicinal Chemistry, 55, 2769-2779.
[19] Mokale, S.N., Elgire, R.D., Sakle, N.S. and Shinde, D.B. (2012) Microwave-assisted synthesis, hypolipidemic and hypoglycemic activity of some nove l2-(4-(2-amino-6-(4-substitutedphenyl)-pyrimidin-4-yl)-phenoxy)-2-methylpro- panoicacid derivatives. Archiv der Pharmazie, 345, 22-27.
[20] Mokale, S.N., Shete, M.T., Shaikh, S.I. and Shinde, D.B. (2012) Synthesis and hypoli-pidemic activity of novel 2-(4-(2-amino-6-(4-substitutedphenyl) pyrimidin-4-yl)-2-substituted phenoxy) acetic acid de-rivatives. Chemical Biology & Drug Design, 79, 548-552.
[21] Bandgar, B.P., Sarangdhar, R.J., Khan, F., Mookkan, J., Shetty, P. and Singh, G. (2011) Synthesis and biological evaluation of orally active hypolipidemic agents. Journal of Medicinal Chemistry, 54, 5915-5926.
[22] Bandgar, B.P., Sarangdhar, R.J., Fruthous, K., Mookkan, J., Chaudhary, S., Chavan, H.V., et al. (2012) Synthesis and biological evaluation of ester prodrugs of Benzafibrate as orally active hypo-lipidemic agents. European Journal of Medicinal Chemistry, 57, 217-224.
[23] Nemoto, H., Kamiya, M., Nakamoto, A., Matsushita, T., Matsumura, K., Hattori, H., et al. (2012) Synthesis of highly water-soluble fibrate derivatives via BGLation. Bioorganic & Medicinal Chemistry Letters, 22, 6425-6428.
[24] Li, W., Jia, H.Y., He, X.H., Shi, W.G. and Zhong, B.H. (2012) Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents. Journal of Enzyme Inhibition and Medicinal Chemistry, 27, 311-318.
[25] Verma, A.K., Singh, H., Satyanarayana, M., Srivastava, S.P., Tiwari, P., Singh, A.B., et al. (2012) Flavone-based novel antidiabetic and antidyslipidemic agent. Journal of Medicinal Chemistry, 55, 4551-4567.
[26] Wang, B., Tang, C., Han, Y., Guo, R.Z., Qian, H. and Huang, W.L. (2012) Synthesis and preliminary antihyperlipidemic activities evaluation of andrographolide derivatives. Medicinal Chemistry, 8, 293-298.
[27] Ogino, M., Nakada, Y., Negoro, N., Itokawa, S., Nishimura, S., Sanada, T., et al. (2011) Discovery of a novel acyl- CoA: Cholesterol acyltransferase inhibitor: The synthesis, biological evaluation, and reduced adrenal toxicity of (4- phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety. Chemical and Pharmaceutical Bulletin, 59, 1369-1375.