CAS: 93957-55-2; Rel-(3S,5R,E)-7-(3-(4-Fluorophenyl)-1-Isopropyl-1H-Indol-2-yl)-3,5-Dihydroxyhept-6-Enoic Acid, Sodium Salt

该化合物是属于STIN类的合成脂低脂剂,主要用于管理超脂性贫血和减少心血管疾病的风险,作为HMG-CoA再生酶抑制剂,在胆固醇生物合成合成物中起着关键作用,其特点是能够降低低密度脂蛋白(LDL)胆固酚水平,同时适度增加高密度的脂质蛋白醇(HDL).氟丙胺钠通常通过口服施用,在胃肠道中被吸收良好,尽管其生物利用率受到肝脏中第一脉冲新陈代谢的影响.该药物一般都受到良好的刺激,但潜在的副作用可能包括肌肉疼痛,肝脏酶异常和胃肠扰动.在肝脏疾病患者或怀孕或哺乳患者中,这种药物是违反的.氟丙酮素经常与饮食改变和生活方式变化相结合,以提高其胆固素管理功能.

结构式图片

欧盟法规

C&L通报

合成工艺路线路线简述

  • 129332-29-2 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Acetonitrile,Water; 3 - 4 H,25 °C -> 35 °C
    标题:Process For Preparation Of Statins With High Syn To Anti Ratio
    参考文献:United States]

    1353637-16-7 = 93957-55-2
    反应条件:1.1 Solvents: Ethanol; 20 - 25 °C1.2 Reagents: Sodium Hydroxide Solvents: Water; 16 H,20 - 25 °C
    标题:Process For The Preparation Of Hmg-Coa Reductase Inhibitors And Intermediates Thereof
    参考文献:World Intellectual Property Organization]

    93957-54-1 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Methanol,Water; 2 H,25 - 35 °C
    标题:An Efficient Industrial Process For The Preparation Of Fluvastatin Sodium
    作者:Reddy,M. S. N.; Reddy,B. K.; Reddy,C. K.; Kumar,M. K.; Rajan,S. T.; Et Al
    参考文献:Oriental Journal Of Chemistry 日期:2007 卷标:23(3) 页码:919-926]

    93957-53-0 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Ethanol,Water; 2 H,Rt
    标题:Synthesis Of (3R,5S,6E)-Rel-7-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indol-2-Yl]-3,5-Dihydroxy-6-Heptenoic Acid Sodium Salt (Fluvastatin Sodium)
    作者:Cai,Zhengyan; Ning,Qi; Zhou,Weicheng
    参考文献:Zhongguo Yiyao Gongye Zazhi 日期:2007 卷标:38(2) 页码:73-75]

    93957-53-0 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Tert-Butyl Methyl Ether,Water; 2.5 H,25 °C1.2 Reagents: Hydrochloric Acid Solvents: Water; Ph 31.3 Reagents: Sodium Hydroxide Solvents: Ethanol,Water; Rt; Overnight,Rt
    标题:Synthesis Of (3R,5S,6E)-Rel-7-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indol-2-Yl]-3,5-Dihydroxy-6-Heptenoic Acid Sodium Salt (1:1) (Fluvastatin Sodium)
    作者:Jin,Hong-Ri; Chen,Xiao-Fang; Yan,Qi-Dong; Yang,Mei-Ling
    参考文献:Hecheng Huaxue 日期:2008 卷标:16(3) 页码:358-361]

    129332-29-2 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Acetonitrile,Water; 25 - 30 °C; 2 H,30 - 35 °C
    标题:Industrial Process For The Preparation Of Fluvastatin Sodium
    参考文献:India]

    = 93957-55-2
    反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Acetonitrile,Water; 30 Min,20 - 25 °C; 1.5 H1.2 Reagents: Sodium Hydroxide Solvents: Water; 20 Min; 3 H,30 - 35 °C1.3 Reagents: Hydrochloric Acid Solvents: Water; Ph 4,0 - 10 °C1.4 Reagents: Dicyclohexylamine Solvents: Acetonitrile; 0 - 10 °C; 2 H,25 - 35 °C
    标题:An Efficient Industrial Process For The Preparation Of Fluvastatin Sodium
    作者:Reddy,M. S. N.; Reddy,B. K.; Reddy,C. K.; Kumar,M. K.; Rajan,S. T.; Et Al
    参考文献:Oriental Journal Of Chemistry 日期:2008 卷标:24(1) 页码:167-174]

    129332-29-2 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Ethanol,Water; Ph 8.5 - 9,Rt -> 10 °C; Ph 8.5 - 9,10 - 15 °C; 1 H,Ph 8.5 - 9,10 - 15 °C; Ph 8.5 - 9,15 °C -> 37 °C; 3 H,Ph 8.5 - 9,37 °C
    标题:Process For The Preparation Of Fluvastatin Sodium And Intermediates
    参考文献:World Intellectual Property Organization]

    129332-29-2 = 93957-55-2 [标题:Reaction Conditions
    标题:Process For The Preparation Of Indole Derivatives
    参考文献:World Intellectual Property Organization]

    129332-29-2 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Methanol,Toluene,Water; 1 - 2 Min,25 - 35 °C; 5 H,25 - 35 °C
    标题:Process For Preparation Of Fluvastatin Sodium Salt
    参考文献:World Intellectual Property Organization]

    129332-29-2 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Acetone,Water; Rt; 5 H,Rt1.2 Reagents: Hydrochloric Acid Solvents: Water; Acidified,Rt1.3 Reagents: Sodium Hydroxide Solvents: Methanol,Dichloromethane; Rt; 15 H,Rt
    标题:Method For The Preparation Of Fluvastatin
    参考文献:Korea]

    194935-03-0 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: Ethanol,Water; 15 °C; 1 H,30 - 35 °C
    标题:Process For Preparation Of Fluvastatin Sodium And Intermediate
    参考文献:India]

    194935-03-0 = 93957-55-2
    反应条件:1.1 Reagents: Sodium Hydroxide Solvents: 2-Methyl-2-Butanol,Water; 6 H,20 °C
    标题:Process For The Preparation Of The Antihyperlipidemic Agent Fluvastatin Sodium By Basic Hydrolysis
    参考文献:European Patent Organization

海关参考信息

专利信息


专利号:WO-2006048893-A3
优先权日:2004-11-05
标 题:A process for synthesis of large particle size statin compounds
发明人:SURI SANJAY; SARIN GURDEEP SINGH
权利人:MOREPEN LAB LTD; SURI SANJAY; SARIN GURDEEP SINGH
摘要:This invention discloses a process for synthesis of with large size statin compounds comprising adding solution of desired statin compound either crystalline or amorphous form, optionally obtained from, their intermediates by known methods, in organic solvent to anti-solvent, under stirring, optionally the solvent was being evaporated, isolating the title compound by centrifugation followed by drying under vacuum. Specifically the process was directed to the synthesis of Atorvastatin calcium and Fluvastatin Sodium.

专利号:US-8269001-B2
优先权日:2005-10-05
标题 :Process for the synthesis of HMG-CoA reductase inhibitors
发明人:CASAR ZDENKO
权利人:CASAR ZDENKO; LEK PHARMACEUTICALS
摘要:A novel synthesis of statins uses Wittig reaction of a heterocyclic core of statin with a lactonized side chain already possessing needed stereochemistry. Any separation of diastereoisomers is performed early in the course of synthesis.

专利号:US-10022366-B2
优先权日:2013-04-23
标 题:Extending and maintaining micropore viability of microneedle treated skin with lipid biosynthesis inhibitors for sustained drug delivery
发明人:STINCHCOMB AUDRA L; GHOSH PRIYANKA
权利人:STINCHCOMB AUDRA L; GHOSH PRIYANKA; UNIV MARYLAND; UNIV KENTUCKY RES FOUND
摘要:Microneedles and their use as a physical skin permeation enhancement technique facilitate drug delivery across the skin in therapeutically relevant concentrations. Micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU) was used to enhance pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin.

专利号:WO-2006021326-A1
优先权日:2004-08-27
标题:Process and intermediates for the selective synthesis of fluvastatin
发明人:ZHU GUORONG; GONG HONGQUAN; BECKER STEFAN
权利人:ZHEJIANG HISUN PHARMACEUTICAL; TIEFENBACHER PHARMACHEMIKALIEN; ZHU GUORONG; GONG HONGQUAN; BECKER STEFAN
摘要:The invention relates to process for the selective preparation of 3-hydroxy-6-dialkoxyphosphoryl-5-oxo-hexanoic acid esters, comprising a first step, in which a methylphosphonic acid dialkylester is treated with a base, and a second step, in which the product of the primary reaction is reacted with an optionally 3-protected 3-hydroxy-1,5-pentanoic diacid ester.

专利号:US-7851624-B2
优先权日:2003-12-24
标题 :Triol form of rosuvastatin and synthesis of rosuvastatin
发明人:NIDDAM-HILDESHEIM VALERIE; BALANOV ANNA; VEINBERG IRENA
权利人:TEVA PHARAMACEUTICAL IND LTD
摘要:Provided is a rosuvastatin triol and its use as a reference standard for analysis of rosuvastatin. Also provided are methods for preparation of rosuvastatin.

专利号:US-8158362-B2
优先权日:2005-03-30
标题:Methods of diagnosing susceptibility to myocardial infarction and screening for an LTA4H haplotype
发明人:HELGADOTTIR ANNA; HAKONARSON HAKON; GULCHER JEFFREY R; GURNEY MARK E
权利人:HELGADOTTIR ANNA; HAKONARSON HAKON; GULCHER JEFFREY R; GURNEY MARK E; DECODE GENETICS EHF
摘要:Polymorphisms in the FLAP and LTA4H gene are shown by genetic association analysis to be susceptibility markers for myocardial infarction (MI) and ACS, as well as stroke and PAOD. Pathway targeting for treatment and diagnostic applications in identifying those who are at risk of developing MI, ACS, stroke or PAOD, in particular are described. The invention also provides methods of prophylaxis therapy for MI in human subjects having a race including black African ancestry by administering to the subject a composition comprising a therapeutically effective amount of MI therapeutic agent that inhibits leukotriene synthesis in vivo. The invention also provides for compositions comprising a leukotriene synthesis inhibitor and a statin and methods of using these compositions to reduce C-reactive protein in a human subject at risk of MI, ACS, stroke and/or PAOD.
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主要参考文献


1: Borgmann SH, Bernardi LS, Rauber GS, Oliveira PR, Campos CE, Monti G, Cuffini SL, Cardoso SG. Solid-state characterization and dissolution properties of Fluvastatin sodium salt hydrates. Pharm Dev Technol. 2013 Mar-Apr;18(2):525-34. doi: 10.3109/10837450.2012.727000. Epub 2012 Oct 4. doi: 10.1016/j.transproceed.2015.10.027. doi: 10.5551/jat.28175. Epub 2015 Jan 16. Chinese. doi: 10.1016/j.pharep.2014.01.002. Epub 2014 Feb 1. doi: 10.4049/jimmunol.1501932. Epub 2016 Jan 15.
7: Galus R, Włodarski K, Malejczyk J, Jóźwiak J. Fluvastatin influences hair color in C57BL/6 mice. Int J Mol Sci. 2013 Jul 10;14(7):14333-45. doi: 10.3390/ijms140714333.
8: Korhonova M, Doricakova A, Dvorak Z. Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human Hepatocytes. PLoS One. 2015 Sep 14;10(9):e0137720. doi: 10.1371/journal.pone.0137720. eCollection 2015.

合成参考文献


参考文献:10.1016/j.bbrc.2023.08.050
摘要:Ikeda Y, Davis MI, Sumita K, Zheng Y, Kofuji S, Sasaki M, Hirota Y, Pragani R, Shen M, Boxer MB, Takeuchi K, Senda T, Simeonov A, Sasaki AT. Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells. Biochemical and Biophysical Research Communications. 2023 Oct;679():116–21. doi: 10.1016/j.bbrc.2023.08.050.
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