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所属专题： 酶化学

• 综述与评论 •

非核苷类HCV NS5B聚合酶抑制剂

伍道春, 何严萍*   

  1. 云南大学化学科学与工程学院 教育部自然资源药物化学重点实验室 昆明 650091
  • 收稿日期:2012-04-01 修回日期:2012-06-01 出版日期:2012-11-24 发布日期:2012-10-23
  • 基金资助:

    国家自然科学基金项目(No.30960459,21262044)资助

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HCV Non-Nucleoside NS5B Polymerase Inhibitors

Wu Daochun, He Yanping   

  1. Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China
  • Received:2012-04-01 Revised:2012-06-01 Online:2012-11-24 Published:2012-10-23
全球约有1.7亿人感染丙型肝炎病毒(HCV),至今尚无有效的疫苗和治疗药物。目前干扰素-α和利巴韦林联用抗HCV 的标准治疗方案存在严重不良反应。近年来,新型抗HCV的研究主要集中于针对病毒感染的特异性靶点寻找新的抑制剂。NS5B聚合酶因其在HCV RNA基因组复制中的关键性作用,是目前抗HCV药物设计的重要靶点之一。NS5B聚合酶抑制剂可分为核苷类抑制剂(NIs)和非核苷类抑制剂(NNIs)。自从第一个NS5B NNIs苯并咪唑类化合物被报道以来,大量不同结合位点NS5B NNIs相继被报道,一些化合物在临床研究中表现出了可喜的疗效。本文综述了苯并噻二嗪类、苯并咪唑类、吲哚类、噻吩羧酸类、喹啉酮类、二氢吡喃类和二酮酸类等 NS5B NNIs的研究进展,旨在为该类抑制剂的开发研究提供参考。
关键词： 丙型肝炎病毒(HCV), 特异性靶向药物, NS5B聚合酶, 非核苷类抑制剂
Hepatitis C virus (HCV) infection has emerged as a significant global public health problem, with an estimated 170 million chronically infected individuals worldwide, and a leading cause of liver transplantation. Currently neither a vaccine nor a therapy with effective broad spectrum mode of action against all genotypes of HCV is available. Current HCV therapy comprising of pegylated interferon α (PEGeIFN-α) in combination with ribavirin has found limited patient compliance due to severe adverse effects. In the past two decades, several approaches have been adopted to inhibit non-structural viral proteins. RNA dependent RNA polymerase coded by NS5B protein is an attractive therapeutic target, since it plays an important role in replicating the HCV RNA genome and the host lacks its functional equivalent. According to its function mechanism and chemical structure, NS5B inhibitors mainly divided into nucleoside inhibitors(NIs) and non-nucleoside inhibitors(NNIs), the latter can bind to less conserved sites outside the active site and impair the enzyme’s catalytic efficiency. Scince the benzimidazole-based compounds were identified as NS5B NNIs, several inhibitors targeting various known binding sites within HCV NS5B polymerase have demonstrated useful efficacy in clinical trials. In this article, the recent progress of NS5B NNIs, such as benzothiadiazines, benzimidazoles, indole analogs, thiophene carboxylic acids, isoquinoline and quinolones, dihydropyranones, diketo acids and so on, is reviewed to provide some useful information for the further research and development of HCV polymerase inhibitors. Contents
1 Introduction
1.1 Gene structure and replicative cycle of HCV
1.2 Structure of HCV NS5B polymerase and its relation ship of activity with RdRp
1.3 NS5B polymerase as an anti-HCV drug target
2 Non-nucleoside inhibitors of HCV NS5B polymerase
2.1 Benzothiadiazine analogs
2.2 Benzimidazole analogs
2.3 Indole analogs
2.4 Thiophene carboxylic acid analogs
2.5 Isoquinoline and quinolone analogs
2.6 Dihydropyranone analogs
2.7 Diketo acid analogs
2.8 The other non-nucleoside inhibitors
3 Conclusion
Key words: HCV, specifically targeted antiviral drugs, NS5B polymerase, non-nucleoside inhibitors Contents

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[1] Kuo G, Choo Q L, Alter H J, Gitnick G L, Redeker A G, Purcell R H, Miyamura T, Dienstag J L, Alter M J, Stevens C E. Science, 1989, 244: 362-364
[2] Thomson B J, Finch R G. Clin. Microbiol. Infect., 2005, 11: 86-94
[3] Lin K, Perni R B, Kwong A D, Lin C. Antimicrob. Agents. Chemother., 2006, 50: 1813-1822
[4] Dusheiko G, Hezode C, Pol S, Goeser T, Bronowicki J, Bourliere M, Buqqisch P, Serfaty L, Berq T, Couziqe P, Benhamou Y, Forestier N, Benqtsson L, Gharakhanian S, Kauffman R, Alam J, Ferenci P, Pawlotsky J M, Zeuzem S. J. Hepatoll., 2008, 48 Suppl 2: 26
[5] Kwo P, Lawitz E, McCone J, Schiff E, Vierling J, Pound D, Davis M, Galati J, Gordon s, Ravendhran N, Rossaro L, Anderson F, Jacobson I, Rubin R, Mukhopadhyay P, Chaudhri E, Pedicone L, Albrecht J. J. Hepatol., 2008, 48 Suppl 2: 372
[6] Crabbe R, Vuagniaux G, Dumont J M, Nicolasmetral V, Marfurt J, Novaroli L. Expert. Opin. Investig. Drugs, 2009, 18: 211-220
[7] Flisiak R, Horban A, Gallay P, Bobardt M, Selvarajah S, WiercinskaDrapalo A, Siwak E, Cielniak I, Higersberger J, Kierkus J, Aeschlimann C, Grosgurin P, NicolasMetral V, Dumont J M, Porchet H, Crabbe R, Scalfaro P. Hepatology, 2008, 47: 817-826
[8] Bartenschlager R, Lohmann V. J. Gen. Virol., 2000, 81: 1631-1648
[9] Modi A A, Liang T. J. Oral. Dis., 2008, 14: 10-14
[10] Honda M, Ping L H, Rijnbrand R C A, Amphlett E, Clarke B, Rowlands D, Lemon S M. Virology, 1996, 222: 31-42
[11] Lin C, Lindenbach B D, Pragai B M, Mccourt D W, Rice C M. J. Virol., 1994, 68: 5063-5073
[12] Dubuisson J, Hsu H H, Cheung R C, Greenberg H B, Russell D G, Rice C M. J. Virol., 1994, 68: 6147-6160
[13] Lohmann V, Korner F, Herian U, Bartenschlager R. J. ViroI., 1997, 71: 8416-8428
[14] Labonte P, Axelrod V, Agarwal A, Aulabaugh A, Amin A, Mak P J. Biol. Chem., 2002, 277: 38838-38846
[15] Bressanelli S, Tomei L, Roussel A, Mathieu M, Francesco R D, Rey F A. Proc. Natl Acad. Sci. USA., 1999, 96: 13034-13039
[16] Liu Y Y, Jiang W W, Pratt J, Rockway T, Harris K, Vasavanonda S, Tripathi R P, Kati W M. Biochemistry, 2006, 45: 11312-11323
[17] De Clercq E. Nature Rev Drug Discov., 2007, 6: 1001- 1018
[18] Dhanak D, Duffy K J, Johnston V K, LinGoerke J, Darcy M, Shaw A N, Gu B, Silverman C, Gates A T, Nonnemacher M R, Earnshaw D L, Casper D J, Kaura A, Baker A, Greenwood C, Gutshall L L, Maley D, DelVecchio A, Macarron R, Hofmann G A, Alnoah Z, Cheng H Y, Chan G, Khandekar R M, Sarisky R T. J. Biol. Chem., 2002, 277: 38322-38327
[19] Shaw A N, Tedesco R, Bambal R, Chai D, Concha N O, Darcy M G, Danak D, Duffy K J, Fitch D M, Gates A, Johnston V K, Keenan R M, LinGoerke J, Liu N, Sarisky R T, Wiggall K J, Zimmerman M N. Bioorg. Med. Chem. Lett., 2009, 19: 4350-4353
[20] Tedesco R, Chai D P, Darcy M G, Danak D, Fitch D M, Gates A, Johnston V K, Keenan R M, LinGoerke J, Sarisky R T, Shaw A N, Valko K L, Wiggall K J, Zimmerman M N, Duffy K J. Bioorg. Med. Chem. Lett., 2009, 19: 4354-4358
[21] Bosse T D, Larson D P, Wanger R, Hutchinson D K, Rockway T W, Kati W M, Liu Y Y, Masse S V, Middleton T, Mo H, Montgomery D A, Jiang W W, Koev G., Kempf D J, Molla A. Bioorg. Med. Chem. Lett., 2008, 18: 568- 570
[22] Bosse T D, Larson D P, Wanger R, Hutchinson D K, Rockway T W, Kati W M, Liu Y Y, Masse S V, Middleton T, Mo H, Montgomery D A, Jiang W W, Koev G., Kempf D J, Molla A. Bioorg. Med. Chem. Lett., 2008, 18: 3887- 3890
[23] Wanger R, Larson D P, David W A B, Bosse T D, Darbyshire J F, Gao Y, Gates B, D, He W P, Henry R F, Hernandez L E, Hutchinson D K, Jiang W W, Kati W M, Klein L L, Koev G, Kohlbrenner W, Krueger A C, Liu J R, Liu Y Y, Long M A, Maring C J, Masse S V, Middleton T, Montgomery D A, Prant J K, Stuart P, Molla A, Kempf D J. J. Med. Chem., 2009, 52: 1659-1669
[24] Randolph J T, Flentge C A, Huang P P, Hutchinson D K, Klein L L, Lim H B, Mondal R, Reisch T, Montgomery D A, Jiang W W, Masse S V, Hernandez L E, Henry R F, Liu Y, Koev G, Kati W M, Stewart K D, Beno D W A, Molla A, Kempf D J. J. Med. Chem., 2009, 52: 3174- 3183
[25] Hutchinson D K, Flentge C A, Donner P L, Wagner R, Maring C J, Kati W M, Liu Y Y, Masse S V, Middleton T, Mo H, Montgomery D, Jiang W W, Koev G, Beno D W A, Stewart K D, Stoll V S, Molla A, Kempf D J. Bioorg. Med. Chem. Lett., 2011, 21: 1876-1879
[26] Vicente J D, Hendricks R T, Smith D B, Fell J B, Fisher J, Spencer S R, Stengel P J, Mohr P, Robinson J E, Blake J F, Hilgenkamp R K, Yee C, Adjabeng G, Elworthy T R, Li J, Wang B H, Bamberg J T, Harris S F, Najera I, Pogam S L, Rajyaguru S, Gloria A I, Alexandrova L, Larrabee S, Brandl M, Briggs A, Sukhtankar S, Farrell R. Bioorg. Med. Chem. Lett., 2009, 19: 5652-5656
[27] Hendricks R T, Fell J B, Blake J F, Fischer J P, Rbinson J E, Spencer S R., Stengel P J, Bernacki A L, Leveque V J P, Pogam S L, Rajyaguru S, Najera I, Josey J A, Harris J R, Swallow S. Bio. Med. Chem., 2009, 19: 3637-3641
[28] Vicente J D, Hendricks R T, Smith D B, Fell J B, Fisher J, Spencer S R, Stengel P J, Mohr P, Robinson J E, Blake J F, Hilgenkamp R K, Yee C, Adjabeng G, Elworthy T R, Tracy J, Chin E, Li J, Wang B H, Bamberg J T, Stephenson R, Oshiro C, Harris S F, Ghate M, Leveque V J P, Najera I, Pogam S L, Rajyaguru S, Gloria A I, Alexandrova L, Larrabee S, Brandl M, Briggs A, Sukhtankar S, Farrell R, Xu B. Bioorg. Med. Chem. Lett., 2009, 19: 3642-3646
[29] Wang G Y, Lei H X, Wang X F, Das D, Hong J, Mackinnon C H, Coulter T S, Montalbetti C A G N, Mears R, Gai X J, Bailey S E, Ruhrmund D, Hooi L, Misialek S, Rajagopalan P T R, Cheng R K Y, Barker J J, Felicetti B, Schonfeld, D L, Stoycheva A, Buckman B O, Kossen K, Seiwert S D, Beigelman L. Bio. Med. Chem., 2009, 19: 4480-4483
[30] Wang G Y, Zhang L G, Wu X M, Das D, Ruhrmund D, Hooi L, Misialek S, Rajagopalan P T R, Buckman B O, Kossen K, Seiwert S D, Beigelman L. Bio. Med. Chem., 2009, 19: 4484-4487
[31] Ruebsam F, Tran C V, Li L S, Kim S H, Xiang A X, Zhou Y, Blazel J K, Sun Z, Dragovich P S, Zhao J, Mcguire H, Murphy D E, Tran M T, Stankovic N, Ellis D A, Gobbi A, Showalter R E, Webber S E, Shah A M, Tsan M, Patel R A, LeBrun L A, Hou H J, Kamran R, Sergeeva M V, Bartkowski D M, Nolan T G, Norris D A, Kirkovsky L. Bioorg. Med. Chem. Lett., 2009, 19: 451-458
[32] Ruebsam F, Murphy D E, Tran C V, Li L S, Zhao J J, Dragovich P S, McGuire H M, Xiang A X, Sun Z X, Ayida B K, Blazel J K, Kim S H, Zhou Y F, Han Q, Kissinger C R, Webber S E, Showalter R E, Shah A M, Tsan M, Patel R A, Thompson P A, LeBrun L A, Hou H J, Kamran R, Sergeeva M V, Bartkowski D M, Nolan T G., Norris D A, Khanduina J, Brooks J, Okamoto E, Kirkovsky L. Bioorg. Med. Chem. Lett., 2009, 19: 6404-6412
[33] Vicente J D, Hendricks R T, Smith D B, Fell J B, Fisher J, Spencer S R, Stengel P J, Mohr P, Robinson J E, Blake J F, Hilgenkamp R K, Zhao J P, Elworthy T R, Tracy J, Chin E, Li J, Lui A, Wang B H, Oshiro C, Harris S F, Ghate M, Leveque V J P, Najera I, Pogam S L, Rajyaguru S, Gloria A I, Alexandrova L, Fitch B, Brandl M, Masjedizadeh M, Wu S Y, Keczer S D, Voronin T. Bioorg. Med. Chem. Lett., 2009, 19: 5648-5651
[34] Donner P L, Xie Q, Pratt J K, Maring C J, Kati W, Jiang W, Liu Y, Koev G, Masse S, Montgomery D, Molla A, Kempf D J. Bioorg. Med. Chem. Lett., 2008, 18: 2735- 2738
[35] Ellis D A, Blazel J K, Tran C V, Ruebsam F, Murphy D E, Li L S, Zhao J J, Zhou Y F, McGuire H M, Xiang A X, Webber S E, Zhao Q, Han Q, Kissinger C R, Lardy M, Gobbi A, Showalter R E, Shah A M, Tsan M, Patel R A, LeBrun L A, Kamran R, Bartkowski D M, Nolan T G, Norris D A, Sergeeva M V, Kirkovsky L. Bioorg. Med. Chem. Lett., 2009, 19: 6047-6052
[36] Hirashima S, Suzuki T, Ishida T, Noji S, Yata S, Ando I, Komatsu M, Ikeda S, Hashimoto H. J. Med. Chem., 2006, 49: 4721-4736
[37] Kukolj G, McGibbon G A, Mckercher G, Marquis M, Lefebvre S, Gauthier J, Goulet S, Poupart M A, Beaulieu P L. J. Biol. Chem., 2005, 280: 39260-39267
[38] Beaulieu P L, Bos M, Bousquet Y, Fazal G, Gauthier J, Gillard J, Gouler S, LaPlante S, Poupart M A, Lefebvre S, McKercher G, Pellerin C, Austel V, Kukolj G. Bioorg. Med. Chem. Lett., 2004, 14: 119-124
[39] Beaulieu P L, Bos M, Bousquet Y, DeRoy P, Fazal G., Gauthier J, Gillard J, Gouler S, McKercher G, Poupart M A, Valois S, Kukolj G. Bioorg. Med. Chem. Lett., 2004, 14: 967-971
[40] Beaulieu P L, Danserau N, Duan J, Garneau M, Gillard J, McKercher G, LaPlante S, Lagacee L, Thauvette L, Kukolj G. Bioorg. Med. Chem. Lett., 2010, 20: 1825-1829
[41] Goulet S, Poupart M A, Gillard J, Poirier M, Kukolj G, Beaulieu P L. Bioorg. Med. Chem. Lett., 2010, 20: 196- 200
[42] Beaulieu P L, Gillard J, Bykowski D, Brochu C, Dansereau N, Duceppe J S, Hache B, Jakalian A, Lagace L, LaPlante S, McKercher G., Moreau E, Perreault S, Stammers T, Thauvette L, Warrington J, Kukolj G. Bioorg. Med. Chem. Lett., 2006, 16: 4987-4993
[43] Beaulieu P L, Jolicoeur E, Gillard J, Brochu C, Coulombe R, Dansereau N, Duan J, Garneau M, Jakalian A, Kuhn P, Lagace L, Laplante S, McKercher G, Perrault S, Poirier M, Poupart M A, Stammers T, Thauvette L, Thavonekham B, Kukolj G. Bioorg. Med. Chem. Lett., 2010, 20: 857-861
[44] Beaulieu P L, Gillard J, Jolicoeur E, Duan J, Garneau M, Kukolj G, Poupart M A. Bioorg. Med. Chem. Lett., 2010, 21: 3658-3663
[45] Laplante S R, Gillard J R, Jakalian A, Aubry N, Coulombe R, Brochu C, Tsantrizos Y S, Poirier M, Kukolj G., Beaulieu P L. J. Am. Chem. Soc., 2010, 132: 15204-15212
[46] Beaulieu P L, Gillard J, Jolicoeur E, Duan J, Garneau M, Kukolj G. Bioorg. Med. Chem. Lett. 2011, 21: 3658-3663
[47] Beaulieu P L, Chabot C, Duan J, Garneau M, Gillard J, Jolicoeur E, Poirier M, Poupart M A, Stammers T A, Kukolj G, Tsantrizos Y S. Bioorg. Med. Chem. Lett., 2011, 21: 3664-3670
[48] Kang L J, Wang L W, Hsu S J, Lee C C, Lee Y C, Wu Y S, Hsu T A, Yueh A, Chao Y S, Chern J H. Bioorg. Med. Chem., 2009, 19: 4134-4138
[49] Haudecoeur R, Belkacem A A, Yi W, Fortune A, Brillet R, Belle C, Nicolle E, Pallier C, Pawlotsky J M, Boum endjel A. J. Med. Chem., 2011, 54: 5395-5402
[50] Ferrari E, He Z, Palermo R E, Huang H C. J. Biol. Chem., 2008, 283: 33893-33901
[51] Anilkumar G, Lesburg C A, Selyutin O, Rosenblum S B, Zeng Q, Jiang Y H, Chan T Y, Vaccaro H, Wang L, Bennett F, Chen K X, Duca J, Gavalas S, Huang Y H, Pinto P, Sannigrahi M, Velazquez S V, Vibulbhan B, Agrawal S, Butkiewicz N, Feld B, Ferrai E, He Z Q, Jiang C K, Palermo R E, Mcmonagle P, Huang H C, Shih N Y, Njoroge G, Kozlowski J A. Bioorg. Med. Chem. Lett., 2011, 21: 5336-5341
[52] LaPorte M G, Draper T L, Miller L E, Blackledge C W, Leister L K, Amparo E, Hussey A R, Young D C, Chunduru S K, Benetatos C A, Rhodes G., Goalsamy A, Herbertz T, Burns C J Condon S M. Bioorg. Med. Chem. Lett., 2010, 20: 2968-2973
[53] LaPorte M G, Jackson R W, Draper T L, Gaboury J A, Galie K, Herbertz T, Hussey A R, Rippin S R, Benetatos C A, Chunduru S K, hristensen J S, Coburn G A, Rizzo C J, Rhodes G, O’Connell J, Howe A Y M, Mansour T, Collett M S, Pevear D C, Young D C, Gao T, Tyrrell D L, Kneteman N M, Burns C J, Condon S M. Chem. Med. Chem., 2008, 3: 1508-1515
[54] Jackson R W, LaPorte M G, Herbertz T, Draper T L, Gaboury J A, Rippin S R, Patel R, Chunduru S K, Benetatos C A, Young D C, Burns C J, Condon S M. Bioorg. Med. Chem. Lett., 2011, 21: 3227 -3231
[55] Zheng X F, Hudyma T W, Martin S W, Bergstrom C, Ding M, He F, Romine J, Poss M A, Kadow J F, Chang C H, Wan J, Witmer M R, Morin P, Camac D M, Sheriff S, Beno B R, Rigat K L, Wang Y K, Fridell R, Lemm J., Qiu D, Liu M, Voss S, Pelosi L, Boberts S B, Gao M, Knipe J, Gentles R G. Bioorg. Med. Chem. Lett., 2011, 21: 2925-2929
[56] Stansfield I, Ercolani C, Mackay A, Conte I, Pompei M, Koch U, Gennari N, Giuliano C, Rowley M, Narjes F. Bioorg. Med. Chem. Lett., 2009, 19: 627-632
[57] Scott J P, Alam M, Bremeyer N, Goodyear A, Lam T, D Wilson R, Zhou G. Org. Process. Res. Dev., 2011, 15: 1116-1123
[58] Narjes F, Crescenzi B, Ferrara M, Habermann J, Colarusso S, Ferreira M R R, Stansfield I, Mackay A C, Conte I, Ercolani C, Zaramella S, Palumbi M C, Meuleman P, Geert L R, Giuliano C, Fiore F, Marco S D, Baiocco P, Koch U, Migliaccio G, Altamura S, Laufer R, Francesco R D, Rowlery M. J. Med. Chem., 2011, 54: 289-301
[59] Chan L, K Das S, Reddy T J, Poisson C, Proulx M, Pereira O, Courchesene M, Roy C, Wang W, Siddiqui A G, Yannopoulos C, Nguyen-Ba N, Labrecque D, Bethell R, Hamel M, Courtemanche -Asselin P, L’Heureux L, David M, Nicolas O, Brunette S, Bilimoria D, Bedard J. Bioorg. Med. Chem. Lett., 2004, 14: 793-796
[60] Chan L, Pereira O, Reddy T J, K Das S, Poisson C, Courchesene M, Proulx M, Siddiqui A, G Yannopoulos C, Nguyen-Ba N, Roy C, Nasturica D, Moinet C, Bethell R, Hamel M, L’Heureux L, David M, Nicolas O, Courtemanche -Asselin P, Brunette S, Bilimoria D, Bedard J. Bioorg. Med. Chem. Lett., 2004, 14: 797-800
[61] Cooper C, Lawitz E J, Ghali P, Rodriguez-Torres M, H. Anderson F, Lee S S, Bedard J, Chauret N, Thibert R, Boivin I, Nicolas O, Proulx, L. J. Hepatol., 2009, 51: 39-46
[62] Hendricks R T, Spencer S R, Blake J F, Fell J B, Fischer J P, Stengel P J, Leveque V J P, LePogam S, Rajyaguru S, Najera I, Josey J A, Swallow S. Bioorg. Med. Chem. Lett., 2009, 19: 410-414
[63] Kumar D V, Rai R, Brameld K A, Somoza J R, Rajagopalan R, Janc J W, Xia Y M, Ton T L, Shaghafi M B, Hu H Y, Lehoux I, To N, Young W B, Green M J. Bioorg. Med. Chem. Lett., 2011, 21: 82-87
[64] Ontoria J M, Rydbeng E H, Marco S D, Tomei L, Attenni B, Malancona S, Hernando J I M, Gennari N, Koch U, Narjes F, Rowley M, Summa V, Caroll S S, Olsen D B, Francesco R D, Altamura S, Migliaccio G, Carfi A. J. Med. Chem., 2009, 52: 5217-5227
[65] Malancona S, Donghi M, Ferrara M, Hernando J M, Pompei M, Pesci S, Ontoria J M, Koch U, Rowley M, Summa V. Bioorg. Med. Chem. Lett., 2010, 18: 2836- 2848
[66] Li H, Tatlock J, Linton A, Gonzalez J, Jewell T, Patel L, Ludlum S, Drowns M, Rahavendran S V, Skor H, Hunter R, Shi S T, Herlihy K J, Parge H, Hickey M, Yu X, Chau F, Nonomiya J, Lewis C. J. Med. Chem., 2009, 52: 1255- 1258
[67] Bhatt A, Gurukumar K R, Basu A, Patel M R, Basu N K, Talele T T. Euro. J. Med. Chem., 2011, 46: 5138-5145
[68] Slater M J, Amphlett E M, Andrews D M, Bravi G, Burton G, Cheasty A G, Corfield J A, Ellis M R, Fenwick R H, Fernandes S, Guidetti R, Haigh D L, Jarvest R L, Lovergrove V L H, Medhurst K J, Parry N R, Price H, Shah P, Singh O M P, Stocker R, Thommes P, Wilknson C, Wonacott A. J. Med. Chem., 2007, 50: 897-900
[69] Agbodjan A A, Cooley B E, Copley R C B, Corfield J A, Flanagan R C, Glover B N, Guidetti R, Haigh D, Howes P D, Jackson M M, Matuoka R T, Medhurst K J, Millar A, Sharp M J, Slater M J, Toczko J F, Xie S. J. Org. Chem., 2008, 73: 3094-3102
[70] Hwu J R, Singha R, Hong S C, Chang Y H, Das A R, Vliegen I, DeClercq E, Neyts. J. Antiviral Res., 2008, 77: 157-162
[71] Neyts J, Clercq E D, Singha R, Chang Y H, Das A R, Chakrabory S K, Hong S C, Tsay S C, Hsu M H, Hwu J R. J. Med. Chem., 2009, 52: 1486-1490
[72] McGowan D, Nyanguile O, Cummings M D, Vendrine S, Vandyck K, Broeck W V D, Boutton C W, Bondt H D, Quirynen L, Amssoms J F B, Last S, Rombaruts K, Tahri A, Hu L L, Delouvroy F, Vermeiren K, Vandercruyssen G, Helm L V D, Cleiren E, Mostmans W, Lory P, Pille G, Emelen K V, Fanning G, Pauwels F, Lin T I, Simmen K, Raboisson P. Bioorg. Med. Chem. Lett., 2009, 19: 2492 -2496
[73] Vandyck K, Cummings M D, Nyanguile O, Boutton C W, Vendeville S, Gowan D M, Devogelaere B, Amssoms K, Last S, Rombauts K, Tahri A, Lory P, Beauchamp D A, Simmen K, Raboisson P. J. Med. Chem., 2009, 52: 4099-4102
[74] Cheng C C, Huang X H, Shipps G W, Wang Y S, Wyss D F, Soucy K A, Jiang C K, Agrawal S, Ferrari E, He Z Q, Huang H C. Acs. Med. Chem. Lett., 2010, 1: 466-471
[75] Cheng C C, ShippsJr G W, Yang Z W, Kawahata N, Lesburg C A, Duca J S, Bandouveres J, Bracken J D, Jiang C H, Agrawal S, Ferrari E, Huang H C. Bioorg. Med. Chem. Lett., 2010, 20: 2119-2124
[76] Gentles R G, Sheriff S, Gentles R G, Wan C H, Kish K, Ding M, Zheng X F, Chupak L, Poss M A, Witmer M R, Morin P, Wang Y K, Rigat K, Lemm J, Voss S, Liu M P, Pelosi L, Roberts S B, Gao M, Kadow J F. Bioorg, Med. Chem. Lett., 2011, 21: 2212-2215
[77] Gentles R G, Ding M, Zheng X F, Chupak L, Poss M A, Beno B R, Pelosi L, Liu M, Lemn J, Wang Y K, Roberts S, Gao M, Kadow J. Bioorg. Med. Chem. Lett., 2011, 21: 3142-3147
[78] Ding Y, Girardet J L, Smith K L, Larson G, Priaro B, Wu J Z, Yao N. Bioorg. Chem., 2006, 34: 26-38
[79] He Y P, Chen F E, Sun G F, Wang Y P, De Clercq E, Balzarini J, Pannecouque C. Bioorg. Med. Chem. Lett., 2004, 14: 3173-3176
[80] Rao Z K, Long J, Li C, Zhang S S, He M, Ou L C, Zheng Y T, He Y P. Monatsh. Chem., 2008, 139: 967-974
[81] He Y P, Long J, Zhang S S, Li C, Lai C C, Zhang C S, Li D X, Zhang D H, Wang H, Cai Q Q, Zheng Y T. Bioorg. Med. Chem. Lett., 2011, 21: 694-697
[82] He Y P, Xia X S, Wu D C, Feng Y, Wang H, Li C. CN 201110352011.5, 2011
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非核苷类HCV NS5B聚合酶抑制剂