MK-608

MK-608
臨床資料
其他名稱	7-Deaza-2’-C-methyladenosine; 7DMA
法律規範狀態
法律規範	美：Investigational New Drug;
识别信息
	IUPAC命名法 (2R,3R,4R,5R)-2-(4-Aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol; ;
CAS号	443642-29-3
PubChem CID	3011893;
ChemSpider	2280834;
UNII	QRR62J6WEF;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID60963208 ;
化学信息
化学式	C12H16N4O4
摩尔质量	280.28 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES C[C@]1([C@@H]([C@H](O[C@H]1n2ccc3c2ncnc3N)CO)O)O;
	InChI InChI=1S/C12H16N4O4/c1-12(19)8(18)7(4-17)20-11(12)16-3-2-6-9(13)14-5-15-10(6)16/h2-3,5,7-8,11,17-19H,4H2,1H3,(H2,13,14,15)/t7-,8-,11-,12-/m1/s1; Key:IRZRJANZDIOOIF-GAJNKVMBSA-N;

MK-608是一种抗病毒药物，属于腺苷类似物（一种核苷类似物（英语：nucleoside analog））。它最初由默克公司开发，用于治疗丙型肝炎。虽然它在动物研究中取得了较好的结果，^[1]^[2]但最终在临床试验中失败。^[3]后来，它被广泛用于体外及动物的抗病毒研究，并显示出对一系列病毒的活性，如骨痛熱症、^[4]蜱传脑炎病毒（英语：tick-borne encephalitis virus）、^[5]脊髓灰質炎病毒、^[6]^[7]以及茲卡病毒。^[8]^[9]

参考文献

^ Carroll SS, Ludmerer S, Handt L, Koeplinger K, Zhang NR, Graham D, et al. Robust antiviral efficacy upon administration of a nucleoside analog to hepatitis C virus-infected chimpanzees. Antimicrobial Agents and Chemotherapy. March 2009, 53 (3): 926–34. PMC 2650549 . PMID 19075052. doi:10.1128/AAC.01032-08.
^ Olsen DB, Davies ME, Handt L, Koeplinger K, Zhang NR, Ludmerer SW, et al. Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents. Antimicrobial Agents and Chemotherapy. February 2011, 55 (2): 937–9. PMC 3028818 . PMID 21115793. doi:10.1128/AAC.00990-10.
^ Arnold JJ, Sharma SD, Feng JY, Ray AS, Smidansky ED, Kireeva ML, et al. Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides. PLOS Pathogens. 2012, 8 (11): e1003030. PMC 3499576 . PMID 23166498. doi:10.1371/journal.ppat.1003030.
^ Schul W, Liu W, Xu HY, Flamand M, Vasudevan SG. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. The Journal of Infectious Diseases. March 2007, 195 (5): 665–74. PMID 17262707. doi:10.1086/511310 .
^ Eyer L, Valdés JJ, Gil VA, Nencka R, Hřebabecký H, Šála M, et al. Nucleoside inhibitors of tick-borne encephalitis virus. Antimicrobial Agents and Chemotherapy. September 2015, 59 (9): 5483–93. PMC 4538560 . PMID 26124166. doi:10.1128/AAC.00807-15.
^ Goris N, De Palma A, Toussaint JF, Musch I, Neyts J, De Clercq K. 2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus. Antiviral Research. March 2007, 73 (3): 161–8. PMID 17055073. doi:10.1016/j.antiviral.2006.09.007.
^ Wu R, Smidansky ED, Oh HS, Takhampunya R, Padmanabhan R, Cameron CE, Peterson BR. Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses. Journal of Medicinal Chemistry. November 2010, 53 (22): 7958–66. PMC 2990348 . PMID 20964406. doi:10.1021/jm100593s.
^ Eyer L, Nencka R, Huvarová I, Palus M, Joao Alves M, Gould EA, et al. Nucleoside Inhibitors of Zika Virus. The Journal of Infectious Diseases. September 2016, 214 (5): 707–11. PMID 27234417. doi:10.1093/infdis/jiw226 .
^ Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J. The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLOS Neglected Tropical Diseases. May 2016, 10 (5): e0004695. PMC 4862633 . PMID 27163257. doi:10.1371/journal.pntd.0004695.

[1] Carroll SS, Ludmerer S, Handt L, Koeplinger K, Zhang NR, Graham D, et al. Robust antiviral efficacy upon administration of a nucleoside analog to hepatitis C virus-infected chimpanzees. Antimicrobial Agents and Chemotherapy. March 2009, 53 (3): 926–34. PMC 2650549 . PMID 19075052. doi:10.1128/AAC.01032-08.

[2] Olsen DB, Davies ME, Handt L, Koeplinger K, Zhang NR, Ludmerer SW, et al. Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents. Antimicrobial Agents and Chemotherapy. February 2011, 55 (2): 937–9. PMC 3028818 . PMID 21115793. doi:10.1128/AAC.00990-10.

[3] Arnold JJ, Sharma SD, Feng JY, Ray AS, Smidansky ED, Kireeva ML, et al. Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides. PLOS Pathogens. 2012, 8 (11): e1003030. PMC 3499576 . PMID 23166498. doi:10.1371/journal.ppat.1003030.

[4] Schul W, Liu W, Xu HY, Flamand M, Vasudevan SG. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. The Journal of Infectious Diseases. March 2007, 195 (5): 665–74. PMID 17262707. doi:10.1086/511310 .

[5] Eyer L, Valdés JJ, Gil VA, Nencka R, Hřebabecký H, Šála M, et al. Nucleoside inhibitors of tick-borne encephalitis virus. Antimicrobial Agents and Chemotherapy. September 2015, 59 (9): 5483–93. PMC 4538560 . PMID 26124166. doi:10.1128/AAC.00807-15.

[6] Goris N, De Palma A, Toussaint JF, Musch I, Neyts J, De Clercq K. 2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus. Antiviral Research. March 2007, 73 (3): 161–8. PMID 17055073. doi:10.1016/j.antiviral.2006.09.007.

[7] Wu R, Smidansky ED, Oh HS, Takhampunya R, Padmanabhan R, Cameron CE, Peterson BR. Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses. Journal of Medicinal Chemistry. November 2010, 53 (22): 7958–66. PMC 2990348 . PMID 20964406. doi:10.1021/jm100593s.

[8] Eyer L, Nencka R, Huvarová I, Palus M, Joao Alves M, Gould EA, et al. Nucleoside Inhibitors of Zika Virus. The Journal of Infectious Diseases. September 2016, 214 (5): 707–11. PMID 27234417. doi:10.1093/infdis/jiw226 .

[9] Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J. The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLOS Neglected Tropical Diseases. May 2016, 10 (5): e0004695. PMC 4862633 . PMID 27163257. doi:10.1371/journal.pntd.0004695.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]