CAS: 850876-88-9; (2R,6S,13As,14Ar,16As,Z)-6-((Tert-Butoxycarbonyl)Amino)-14A-((Cyclopropylsulfonyl)Carbamoyl)-5,16-Dioxo-1,2,3,5,6,7,8,9,10,11,13A,14,14A,15,16,16A-Hexadecahydrocyclopropa[e]Pyrrolo[1,2-A][1,4]Diazacyclopentadecin-2-Yl 4-Fluoroisoindoline-2-Carboxylate
该化合物是丙型肝炎病毒(HCV)NS3/4A蛋白质的强力和选择性抑制剂,对基因型1具有很高的功效,其行动机制包括阻止病毒性聚蛋白加工,从而抑制病毒复制.Danoprevir展示了有利的药用植物遗传特性,包括口服生物利用率和持续血浆浓度,支持一次或两次每日剂量.临床和临床研究显示抗药性低,抗病毒活动强劲,成为综合疗法的有前途的候选方.其化学结构被优化,以加强对蛋白质活性网站的约束性,亲近性和特殊性.Danoprevir正在接受研究,以便用于HCV治疗疗法,特别是无脑结合疗法.
- 英文名称(2R,6S,13As,14Ar,16As,Z)-6-((Tert-Butoxycarbonyl)Amino)-14A-((Cyclopropylsulfonyl)Carbamoyl)-5,16-Dioxo-1,2,3,5,6,7,8,9,10,11,13A,14,14A,15,16,16A-Hexadecahydrocyclopropa[e]Pyrrolo[1,2-A][1,4]Diazacyclopentadecin-2-Yl 4-Fluoroisoindoline-2-Carboxylate
- 中文名称丹诺普韦
- IUPAC名称(2R,6S,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-14a-((cyclopropylsulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl 4-fluoroisoindoline-2-carboxylate
- 其它别名4-Fluoro-1,3-dihydro-2H-isoindole-2-carboxylic acid (2R,6S,13aS,14aR,16aS)-14a-[[(cyclopropylsulfonyl)amino]carbonyl]-6-[[(1,1-dimethylethoxy)carbonyl]amino]-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydro-5,16-diox°Cyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl ester; Danoprevir
- CAS编号850876-88-9
- MFCD编号:MFCD16038038
- EINECS号:0
- FDA UNII编号:911Z9PCQ5F
- 分子式:C35H46FN5O9S
- 分子量:731.84
- 产品CID: 1844264
- 产品分类生物化工 → 抑制剂 → 蛋白酶体(Proteases)
- 相似结构搜索
- InChIKey: ZVTDLPBHTSMEJZ-OBKPAHBMSA-N
- ZVTDLPBHTSMEJZ-AIYSODCISA-N…
- 计算化学: 氢键受体数10.0氢键供体数3.0可旋转键数8.0
物理性质
- 熔点>165°C (分解)
- 密度1.4±0.1 g/cm3
- pKa:4.43±0.60(预测)
- PSA:199.37
- LogP:1.12
- 折射率1.622
- 溶解性Acetone (Slightly), DMSO (Slightly), Methanol (Slightly)
- 外观形态白色至浅米色固体
- 储存条件-20°C 冷藏
- 产品应用该化合物是丙型肝炎病毒(HCV)NS3/4A蛋白抑制器,抗乙型丙型丙肝病毒(乙型乙型肝病毒)的抗药性抑制剂为0.2-3.5纳米;对乙型,1B,4,5和6型丙丙型乙肝病毒的抗血压抑制剂浓度约为10倍;对体外体内抗病毒性活性很强,对HH-7衍生肝炎细胞的HCFV基因型1B类抗血清浓度为1.8 NMNM;DANOPREIR显示持续目标接触,对NS3/4A蛋蛋白质的抑制在最初约束后5小时以上;对79个无关的蛋白1A,1 B,4 , 5 和 3B型乙基蛋白型乙类,2B,3 和3A的细胞地表感应器没有抑制力.在活性体内对79种无阻力的血清,离子,电管,运输器或细胞表面感应体内施压30毫克/千克的细胞内,但对活性肝脏和猴子的DANORPREVIR的肝浓度达到30毫克的浓度足以消除HCVI的血球的肝浓缩的肝素.
MSDS等安全信息
上下游产品
CAS号154350-29-5 环丙磺酰胺合成工艺路线路线简述
- 合成目标产物 Danoprevir 主要起始原料 Cyclopropanesulfonamide And Ethanamine, N-[(3,5-Dichlorophenyl)Methylene]-2,2-Diethoxy-
- 154350-29-5 + 924304-75-6 = 850876-88-9
反应条件:1.1 Reagents: 1,1′-Carbonyldiimidazole Solvents: Dimethylformamide; 2 H,50 °C; 50 °C -> Rt1.2 Reagents: 1,8-Diazabicyclo[5.4.0]Undec-7-Ene; Rt; 50 °C
标题:Discovery Of Danoprevir (Itmn-191/r7227),A Highly Selective And Potent Inhibitor Of Hepatitis C Virus (Hcv) Ns3/4A Protease
作者:Jiang,Yutong; Andrews,Steven W.; Condroski,Kevin R.; Buckman,Brad; Serebryany,Vlad; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2014 卷标:57(5) 页码:1753-1769]
127168-78-9 + 13726-69-7 + 154350-29-5 + 259214-56-7 + 530-62-1 + 300831-21-4 = 850876-88-9
反应条件:1.1R:Etn(Pr-I)2,R:S:Dmf,0°C; 16 H,0°C -> Rt2.1R:HCL,S:Dioxane,90 Min,Rt2.2R:Etn(Pr-I)2,R:S:Dmf,Rt -> 0°C; 0°C; Overnight,0°C -> Rt3.1C:203714-71-0,S:Clch2Ch2Cl,16 H,50°C4.1S:Ch2Cl2,25°C4.2S:Ch2Cl2,25°C; 25°C4.3R:Lioh h2O,S:H2O,S:Meoh,S:Thf,Rt5.1R:Diimidazolyl Ketone,S:Dmf,2 H,50°C; 50°C -> Rt5.2R:Dbu,Rt; 50°C
标题:Discovery Of Danoprevir (Itmn-191/r7227),A Highly Selective And Potent Inhibitor Of Hepatitis C Virus (Hcv) Ns3/4A Protease
作者:By Jiang,Yutong Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2014 卷标:57(5) 页码:1753-1769]
74844-91-0 + 154350-29-5 + 1279037-85-2 + 7693-46-1 + 300831-21-4 + 924305-06-6 = 850876-88-9
反应条件:1.1R:Diimidazolyl Ketone,S:Thf,1 H,Reflux; Reflux -> Rt1.2R:Dbu,S:Thf,Rt; 24 H,Rt1.3R:HCL,S:H2O,Ph 12.1R:F3Cco2H,S:Ch2Cl2,2 H,Rt2.2R:HCL,S:Et2O1.1R:C5H5N,S:Ch2Cl2,0°C; 20 Min,0°C2.1R:Etn(Pr-I)2,S:Ch2Cl2,0°C; 20 Min,0°C3.1R:HCL,S:Dioxane,2 H,Rt4.1R:R:Etn(Pr-I)2,S:Ch2Cl2,S:Dmf,0°C; 20 Min,0°C5.1R:Lioh,S:H2O,S:Meoh,S:Thf,Overnight,Rt5.2R:HCL,S:H2O6.1R:R:Etn(Pr-I)2,S:Ch2Cl2,S:Dmf,0°C; 30 Min,0°C; 0°C -> Rt; 24 H,Rt7.1C:918870-76-5,S:Clch2Ch2Cl,50°C; 50°C -> 70°C; 1.5 H,70°C; 10 H,70°C
标题:Drug Resistance Against: Hcv Ns3/4A Inhibitors Is Defined By The Balance Of Substrate Recognition Versus Inhibitor Binding
作者:By Romano,Keith P. Et Al
参考文献:Proceedings Of The National Academy Of Sciences Of The United States Of America 日期:2010 卷标:20986-20991 页码:S20986/1-S20986/5]
1338580-61-2 = 850876-88-9
反应条件:1.1 Catalysts: (Sp-5-41)-[1,3-Bis(2,4,6-Trimethylphenyl)-2-Imidazolidinylidene]Dichloro[[5-[(Di... Solvents: 1,2-Dichloroethane; 50 °C; 50 °C -> 70 °C; 1.5 H,70 °C; 10 H,70 °C
标题:Drug Resistance Against: Hcv Ns3/4A Inhibitors Is Defined By The Balance Of Substrate Recognition Versus Inhibitor Binding
作者:Romano,Keith P.; Ali,Akbar; Royer,William E.; Schiffer,Celia A.
参考文献:Proceedings Of The National Academy Of Sciences Of The United States Of America 日期:2010 卷标:107(49) 页码:20986-20991
环丙磺酰胺,(1S,4R,6S,14S,18R)-14-Tert-Butoxycarbonylamino-18-(4-Fluoro-1,3-Dihydro-Isoindole-2-Carbonyloxy)-2,15-Dioxo-3,16-Diaza-Tricyclo[14.3.0.04,6]Nonadec-7-Ene-4-Carboxylic Acid置于乙酸酐,Sodium Carbonate,Potassium Carbonate体系中,用 四氢呋喃 作为反应溶剂,化学反应 25.5H,反应生成 丹诺瑞韦
参考文献: New Ruthenium Complexes As Catalysts For Metathesis Reactions[fr] Nouveaux Complexes Du Ruthénium Comme Catalyseurs Pour Des Réactions De Métathèse
标题: New Ruthenium Complexes As Catalysts For Metathesis Reactions[fr] Nouveaux Complexes Du Ruthénium Comme Catalyseurs Pour Des Réactions De Métathèse
摘要:这项发明涉及公式(i)的新型重排催化剂,以及制备这些催化剂的方法,以及它们在重排反应中的应用,如环闭合或交叉重排.该发明还涉及一种制造公式(vii)的大环化合物的方法,这些化合物有望作为hcv蛋白酶抑制剂有用.
专利信息
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.
专利号:US-11285169-B2
优先权日:2013-03-13
标题 :Methods for modulating chemotherapeutic cytotoxicity
发明人：ROBERTS DAVID D; SOTO PANTOJA DAVID R
权利人:US HEALTH
摘要:Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.
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供应商参考报价(招募中)
品牌试剂参考报价(招募中)
📌 第三方产品分析报告
主要参考文献
1: Markham A, Keam SJ. Danoprevir: First Global Approval. Drugs. 2018 Aug;78(12):1271-1276. doi: 10.1007/s40265-018-0960-0.
14:2759-2774. doi: 10.2147/DDDT.S254754.
3: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Protease Inhibitors (HCV). 2022 Jan 25. 99(48):e23357. doi: 10.1097/MD.0000000000023357.
合成参考文献
摘要:S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
📝 需求与反馈
尽可能描述清楚需求与问题信息
