CAS: 877130-28-4; (R)-6-Cyclopentyl-6-(2-(2,6-Diethylpyridin-4-yl)Ethyl)-3-((5,7-Dimethyl-[1,2,4]Triazolo[1,5-A]Pyrimidin-2-yl)Methyl)-4-Hydroxy-5,6-Dihydro-2H-Pyran-2-One

该化合物是一种抗病毒化合物,主要因其在治疗丙型肝炎病毒(HCV)感染方面的潜在用途而受到调查,属于非核侧聚合酶抑制剂类别,通过干扰病毒RNA聚合酶,从而阻止病毒复制.Filibuvir的化学结构包括一种独特的功能群体安排,有助于其活动和对丙型肝炎的选择性.它在各种临床前科和临床研究中表现出了效力,表明混合疗法有望提高治疗结果.Filibuvir的药用植物特性,如吸收,配送,代谢和排泄,对于治疗应用至关重要,影响剂量疗法和潜在副作用.与许多抗病毒剂一样,抗药性发展是一个关切问题,需要不断开展研究,以便在临床环境中优化使用.

结构式图片

物理性质

MSDS等安全信息

上下游产品

5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde 6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-3H-pyran-2,4-dione (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-dihydro-2H-pyran-2,4(3H)-dione dibenzoyl-L-tartaric acid salt of (R)-6-cyclopentyl-6-(2,6-diethylpyridin-4-yl)ethyl-4-hydroxy-5,6-dihydropyran-2-one

合成工艺路线路线简述

  • 55293-96-4 + 927889-49-4 = 877130-28-4
    反应条件:1.1 Reagents: Hantzsch Ester Solvents: Acetic Acid,Methanol,Tetrahydrofuran; 6 H,40 °C
    标题:Synthesis Of Filibuvir. Part Iii. Development Of A Process For The Reductive Coupling Of An Aldehyde And A β-Keto-Lactone
    作者:Ide,Nathan D.; Et Al
    参考文献:Organic Process Research & Development 日期:2014 卷标:18(1) 页码:45-56]

    = 877130-28-4
    反应条件:1.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; -30 °C
    标题:Synthesis Of Filibuvir. Part Ii. Second-Generation Synthesis Of A 6,6-Disubstituted 2H-Pyranone Via Dieckmann Cyclization Of A β-Acetoxy Ester
    作者:Peng,Zhihui; Et Al
    参考文献:Organic Process Research & Development 日期:2014 卷标:18(1) 页码:36-44]

    55293-96-4 = 877130-28-4
    反应条件:1.1 Catalysts: Piperidine Solvents: Acetic Acid1.2 Reagents: Hydrogen Catalysts: Palladium2.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; -30 °C
    标题:Synthesis Of Filibuvir. Part Ii. Second-Generation Synthesis Of A 6,6-Disubstituted 2H-Pyranone Via Dieckmann Cyclization Of A β-Acetoxy Ester
    作者:Peng,Zhihui; Et Al
    参考文献:Organic Process Research & Development 日期:2014 卷标:18(1) 页码:36-44]

    877133-54-5 = 877130-28-4
    反应条件:1.1 Reagents: Tetrabutylammonium Chloride,Methyldicyclohexylamine Catalysts: Palladium Diacetate Solvents: Dimethylacetamide; 12 H,90 °C1.2 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol2.1 Reagents: 1,1′-Carbonyldiimidazole,Hydrochloric Acid Solvents: Tert-Butyl Methyl Ether,Water2.2 Reagents: Potassium Carbonate Solvents: Methanol3.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C3.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    1035267-63-0 = 877130-28-4
    反应条件:1.1 Reagents: Phosphorus Tribromide Solvents: Dichloromethane2.1 Reagents: Tetrabutylammonium Chloride,Methyldicyclohexylamine Catalysts: Palladium Diacetate Solvents: Dimethylacetamide; 12 H,90 °C2.2 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol3.1 Reagents: 1,1′-Carbonyldiimidazole,Hydrochloric Acid Solvents: Tert-Butyl Methyl Ether,Water3.2 Reagents: Potassium Carbonate Solvents: Methanol4.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C4.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    55293-96-4 = 877130-28-4
    反应条件:1.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C1.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    37517-78-5 + 927889-47-2 = 877130-28-4
    反应条件:1.1 Reagents: 1,1′-Carbonyldiimidazole,Hydrochloric Acid Solvents: Tert-Butyl Methyl Ether,Water1.2 Reagents: Potassium Carbonate Solvents: Methanol2.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C2.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    141-82-2 = 877130-28-4
    反应条件:1.1 Reagents: Methanesulfonic Acid,Propylphosphonic Anhydride Solvents: Toluene2.1 Catalysts: Piperidine Solvents: Acetic Acid2.2 Reagents: Hydrogen Catalysts: Palladium3.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; -30 °C
    标题:Synthesis Of Filibuvir. Part Ii. Second-Generation Synthesis Of A 6,6-Disubstituted 2H-Pyranone Via Dieckmann Cyclization Of A β-Acetoxy Ester
    作者:Peng,Zhihui; Et Al
    参考文献:Organic Process Research & Development 日期:2014 卷标:18(1) 页码:36-44]

    877133-49-8 + 100-51-6 = 877130-28-4
    反应条件:1.1 Reagents: 1,1′-Carbonyldiimidazole2.1 Reagents: Tetrabutylammonium Chloride,Methyldicyclohexylamine Catalysts: Palladium Diacetate Solvents: Dimethylacetamide; 12 H,90 °C2.2 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol3.1 Reagents: 1,1′-Carbonyldiimidazole,Hydrochloric Acid Solvents: Tert-Butyl Methyl Ether,Water3.2 Reagents: Potassium Carbonate Solvents: Methanol4.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C4.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    1115035-61-4 = 877130-28-4
    反应条件:1.1 Reagents: Phosphoric Tribromide Solvents: Dimethylformamide; 120 °C2.1 Reagents: Tetrabutylammonium Chloride,Methyldicyclohexylamine Catalysts: Palladium Diacetate Solvents: Dimethylacetamide; 12 H,90 °C2.2 Reagents: Hydrogen Catalysts: Palladium Solvents: Ethanol3.1 Reagents: 1,1′-Carbonyldiimidazole,Hydrochloric Acid Solvents: Tert-Butyl Methyl Ether,Water3.2 Reagents: Potassium Carbonate Solvents: Methanol4.1 Reagents: Pyridine,Borane Solvents: Methanol; -25 °C -> 0 °C; 3 H,0 °C4.2 Reagents: Water; 30 Min,0 °C
    标题:Synthetic Route Optimization Of Pf-00868554,An Hcv Polymerase Inhibitor In Clinical Evaluation
    作者:Johnson,Sarah; Et Al
    参考文献:Synlett 日期:2010 卷标:(5) 页码:796-800]

    927889-47-2 = 877130-28-4
    反应条件:1.1 Reagents: 1,1′-Carbonyldiimidazole Catalysts: 4-(Dimethylamino)Pyridine Solvents: Tetrahydrofuran1.2 -2.1 Reagents: Methanesulfonic Acid,Propylphosphonic Anhydride Solvents: Toluene3.1 Catalysts: Piperidine Solvents: Acetic Acid3.2 Reagents: Hydrogen Catalysts: Palladium4.1 Reagents: Lithium Bis(Trimethylsilyl)Amide Solvents: Tetrahydrofuran; -30 °C
    标题:Synthesis Of Filibuvir. Part Ii. Second-Generation Synthesis Of A 6,6-Disubstituted 2H-Pyranone Via Dieckmann Cyclization Of A β-Acetoxy Ester
    作者:Peng,Zhihui; Et Al
    参考文献:Organic Process Research & Development 日期:2014 卷标:18(1) 页码:36-44
📜在 哌啶,Palladium On Activated Charcoal,溶剂黄146,Lithium Hexamethyldisilazane体系中,用 四氢呋喃 作为反应溶剂,化学反应生成 (R)-6-环戊基-6-[2-(2,6-二乙基吡啶-4-基)乙基]-3-[(5,7-二甲基-[1,2,4]三唑并[1,5-A]嘧啶-2-基)甲基]-4-羟基-5,6-二氢-2H-吡喃-2-酮
参考文献:非氟布韦的合成.第二部分 通过β-乙氧基酯的dieckmann环化反应第二代合成6,6-二取代的2 H-吡喃酮
标题:非氟布韦的合成.第二部分 通过β-乙氧基酯的dieckmann环化反应第二代合成6,6-二取代的2 H-吡喃酮
摘要:本文描述了将恶唑烷酮(3)转化为β-酮内酯(5)的改进顺序.引起这一变化的主要驱动力是在分子内环化反应中产生β-酮内酯时观测到适度和可变的产率.将环化底物从恶唑烷酮改为烷基酯可显着改善环化作用,并改善炔烃加氢反应.还描述了用于甲醇分解和形成中间盐的最佳底物的选择.
DOI:10.1021/op400236R

海关参考信息

专利信息


专利号:US-12383499-B2
优先权日:2018-01-01
标题:Scale up synthesis of silicasome nanocarriers
发明人：NEL ANDRE E; MENG HUAN; LIU XIANGSHENG
权利人:UNIV CALIFORNIA
摘要:In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).

专利号:US-9573939-B2
优先权日:2011-09-08
标题:Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
发明人：MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; DAI XING; LIU HONG; HE SHUWEN; DANG QUN
权利人:MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; DAI XING; LIU HONG; HE SHUWEN; DANG QUN; MERCK SHARP & DOHME; MSD ITALIA SRL
摘要:The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

专利号:US-2016130259-A1
优先权日:2013-06-24
标题 :Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
发明人：LIU HONG; DAI XING; PALANI ANANDAN; HE SHUWEN; NARGUND RAVI; XIAO DONG; DANG QUN; PENG XUANJIA; LI PENG
权利人:MERCK SHARP & DOHME
摘要:The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

专利号:US-9364482-B2
优先权日:2013-06-24
标 题 :Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
发明人：DAI XING; LIU HONG; PALANI ANANDAN; HE SHUWEN; NARGUND RAVI; XIAO DONG; ZORN NICOLAS; DANG QUN; MCCOMAS CASEY C; PENG XUANJIA; LI PENG; SOLL RICHARD
权利人:MERCK SHARP & DOHME
摘要:The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. (I)

专利号:US-9265773-B2
优先权日:2011-09-08
标题 :Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases
发明人：MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; HE SHUWEN; DAI XING; LIU HONG; LAI ZHONG; LONDON CLARE; XIAO DONG; ZORN NICOLAS; NARGUND RAVI
权利人:MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; HE SHUWEN; DAI XING; LIU HONG; LAI ZHONG; LONDON CLARE; XIAO DONG; ZORN NICOLAS; NARGUND RAVI; MERCK SHARP & DOHME; MSD ITALIA SRL
摘要:The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

专利号:US-9549917-B2
优先权日:2011-09-08
标 题 :Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases
发明人：MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; DAI XING; LIU HONG; HE SHUWEN; LAI ZHONG; DANG QUN; ZORN NICOLAS
权利人:MCCOMAS CASEY C; LIVERTON NIGEL J; HABERMANN JOERG; KOCH UWE; NARJES FRANK; LI PENG; PENG XUANJIA; SOLL RICHARD; WU HAO; PALANI ANANDAN; DAI XING; LIU HONG; HE SHUWEN; LAI ZHONG; DANG QUN; ZORN NICOLAS; MERCK SHARP & DOHME
摘要:The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

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主要参考文献


1: Beaulieu PL. Filibuvir, a non-nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection. IDrugs. 2010 Dec;13(12):938-48. 13(4):364-75. 54(1):50-9. doi: 10.1002/hep.24342. 56(3):1331-41. doi: 10.1128/AAC.05611-11. Epub 2011 Dec 27.
5: Wang H, Guo C, Chen BZ, Ji M. Computational study on the drug resistance mechanism of HCV NS5B RNA-dependent RNA polymerase mutants V494I, V494A, M426A, and M423T to Filibuvir. Antiviral Res. 2015 Jan;113:79-92. doi: 10.1016/j.antiviral.2014.11.005. Epub 2014 Nov 15. 56(2):830-7. doi: 10.1128/AAC.05438-11. Epub 2011 Dec 5.
7: Strohmeyer HE, Sluggett GW. Determination and control of TEMPO, a potentially genotoxic free radical reagent used in the synthesis of filibuvir. J Pharm Biomed Anal. 2012 Mar 25;62:216-9. doi: 10.1016/j.jpba.2011.12.036. Epub 2012 Jan 8. 8(44):41570-41578. doi: 10.1021/acsomega.3c05637.

合成参考文献


摘要:S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
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