浅谈阿托伐他汀的作用机理及合成
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摘要
阿托伐他汀是一种他汀类的药物,在降低心血管疾病和死亡风险方面,有着高效、安全的长期临床效益。本文对阿托伐他汀的药动力学机理进行分析,在此基础上,对阿托伐他汀合成路径研究综述。研究表明:阿托伐他汀主要有线性、收敛性两种合成策略,Paal-Knorr吡咯法通常被认为是最广泛的使用方法。
Atorvastatin is a statin drug with high-efficiency, safe long-term clinical benefits in reducing the risk of cardiovascular disease and death. In this paper, the pharmacokinetic mechanism of atorvastatin was analyzed, and on this basis, the research on the synthesis pathway of atorvastatin was reviewed. Studies have shown that atorvastatin has two linear and astringent synthetic strategies, and the Paal-Knorr pyrrole method is generally considered to be the most widely used method.
Atorvastatin is a statin drug with high-efficiency, safe long-term clinical benefits in reducing the risk of cardiovascular disease and death. In this paper, the pharmacokinetic mechanism of atorvastatin was analyzed, and on this basis, the research on the synthesis pathway of atorvastatin was reviewed. Studies have shown that atorvastatin has two linear and astringent synthetic strategies, and the Paal-Knorr pyrrole method is generally considered to be the most widely used method.
引文
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[5]Christians U,Jacobsen W,Floren L C.Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients:are the statins mechanistically similar?[J].Pharmacology&Therapeutics,1998,80(1):1-34.
[6]Kim M S,Jin S J,Kim J S,et al.Preparation,characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent(SAS)process[J].European Journal of Pharmaceutics&Biopharmaceutics,2008,69(2):454-465.
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[8]Isanbor C,O’Hagan D.Fluorine in medicinal chemistry:A review of anti-cancer agents☆[J].Cheminform,2006,37(30):303-319.
[9]Lynch J E,Volante R P,Wattley R V,et al.Synthesis of an HMG-CoAreductase inhibitor,a diastereoselective aldol approach[J].Tetrahedron Letters,1987,28(13):1385-1387.
[10]Mathew J,Sambasivam G,Sridharan M,et al.Process for the synthesis of atorvastatin form v and phenylboronates as intermediate compounds:U.S.Patent 6,867,306[P].2005-3-15.
[11]Mothana B,Boyd R J.A density functional theory study of the mechanism of the Paal-Knorr pyrrole synthesis[J].Journal of Molecular Structure Theochem,2007,811(1):97-107.
[12]Alaupovic P,Heinonen T,Shurzinske L,et al.Effect of a new HMG-CoAreductase inhibitor,atorvastatin,on lipids,apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels[J].Atherosclerosis,1997,133(1):123-33.
[2]Radosavljevi B,Biro G.A centenary of the Nobel Prize for medicine and physiology[J].Srpski arhiv za celokupno lekarstvo,2001,129(7-8):222-226.
[3]LIANG J,ZHANG S.Research Progress and Evaluation of Clinical Application of Proton-pump Inhibitors[J].Evaluation and Analysis of Drug-use in Hospital of China,2001,4.
[4]Igel M,Sudhop T,Bergmann K V.Metabolism and drug interactions of3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors(statins)[J].European Journal of Clinical Pharmacology,2001,57(5):357-364.
[5]Christians U,Jacobsen W,Floren L C.Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients:are the statins mechanistically similar?[J].Pharmacology&Therapeutics,1998,80(1):1-34.
[6]Kim M S,Jin S J,Kim J S,et al.Preparation,characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent(SAS)process[J].European Journal of Pharmaceutics&Biopharmaceutics,2008,69(2):454-465.
[7]Vasantray V A,Pranlal D V.A process for preparation of amorphous form of atorvastatin hemi-calcium salt[J].2009.
[8]Isanbor C,O’Hagan D.Fluorine in medicinal chemistry:A review of anti-cancer agents☆[J].Cheminform,2006,37(30):303-319.
[9]Lynch J E,Volante R P,Wattley R V,et al.Synthesis of an HMG-CoAreductase inhibitor,a diastereoselective aldol approach[J].Tetrahedron Letters,1987,28(13):1385-1387.
[10]Mathew J,Sambasivam G,Sridharan M,et al.Process for the synthesis of atorvastatin form v and phenylboronates as intermediate compounds:U.S.Patent 6,867,306[P].2005-3-15.
[11]Mothana B,Boyd R J.A density functional theory study of the mechanism of the Paal-Knorr pyrrole synthesis[J].Journal of Molecular Structure Theochem,2007,811(1):97-107.
[12]Alaupovic P,Heinonen T,Shurzinske L,et al.Effect of a new HMG-CoAreductase inhibitor,atorvastatin,on lipids,apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels[J].Atherosclerosis,1997,133(1):123-33.