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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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General Review Article

Triazolopyrimidine Nuclei: Privileged Scaffolds for Developing Antiviral Agents with a Proper Pharmacokinetic Profile

Author(s): Tommaso Felicetti, Maria Chiara Pismataro, Violetta Cecchetti, Oriana Tabarrini* and Serena Massari*

Volume 29, Issue 8, 2022

Published on: 23 August, 2021

Page: [1379 - 1407] Pages: 29

DOI: 10.2174/0929867328666210526120534

Price: $65

Abstract

Viruses are a continuing threat to global health. The lack or limited therapeutic armamentarium against some viral infections and increasing drug resistance issues make the search for new antiviral agents urgent. In recent years, a growing literature highlighted the use of triazolopyrimidine (TZP) heterocycles in the development of antiviral agents, with numerous compounds that showed potent antiviral activities against different RNA and DNA viruses. TZP core represents a privileged scaffold for achieving biologically active molecules, thanks to: i) the synthetic feasibility that allows to variously functionalize TZPs in the different positions of the nucleus, ii) the ability of TZP core to establish multiple interactions with the molecular target, and iii) its favorable pharmacokinetic properties. In the present review, after mentioning selected examples of TZP-based compounds with varied biological activities, we will focus on those antivirals that appeared in the literature in the last 10 years. Approaches used for their identification, the hit-to-lead studies, and the emerged structure-activity relationship will be described. A mention of the synthetic methodologies to prepare TZP nuclei will also be given. In addition, their mechanism of action, the binding mode within the biological target, and pharmacokinetic properties will be analyzed, highlighting the strengths and weaknesses of compounds based on the TZP scaffold, which is increasingly used in medicinal chemistry.

Keywords: Triazolopyrimidines, viruses, small molecules, antiviral drugs, pharmacokinetic properties, medicinal chemistry, viral polymerase.

« Previous Next »
[1]
Renyu, Q.; Yuchao, L.; Kandegama, W.M.W.W.; Qiong, C.; Guangfu, Y. Recent applications of triazolopyrimidine-based bioactive compounds in medicinal and agrochemical chemistry. Mini Rev. Med. Chem., 2018, 18(9), 781-793.
[http://dx.doi.org/10.2174/1389557517666171101112850] [PMID: 29090667]
[2]
Johnson, T.C.; Martin, T.P.; Mann, R.K.; Pobanz, M.A. Penoxsulam--structure-activity relationships of triazolopyrimidine sulfonamides. Bioorg. Med. Chem., 2009, 17(12), 4230-4240.
[http://dx.doi.org/10.1016/j.bmc.2009.02.010] [PMID: 19464188]
[3]
DeBoer, G.J.; Thornburgh, S.; Gilbert, J.; Gast, R.E. The impact of uptake, translocation and metabolism on the differential selectivity between blackgrass and wheat for the herbicide pyroxsulam. Pest Manag. Sci., 2011, 67(3), 279-286.
[http://dx.doi.org/10.1002/ps.2062] [PMID: 21104793]
[4]
Chen, C.N.; Chen, Q.; Liu, Y.C.; Zhu, X.L.; Niu, C.W.; Xi, Z.; Yang, G.F. Syntheses and herbicidal activity of new triazolopyrimidine-2-sulfonamides as acetohydroxyacid synthase inhibitor. Bioorg. Med. Chem., 2010, 18(14), 4897-4904.
[http://dx.doi.org/10.1016/j.bmc.2010.06.015] [PMID: 20598554]
[5]
Mazurov, A.V. Menshikov MYu; Leytin, V.L.; Tkachuk, V.A.; Repin, V.S. Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidil. FEBS Lett., 1984, 172(2), 167-171.
[http://dx.doi.org/10.1016/0014-5793(84)81119-9] [PMID: 6086387]
[6]
Jacobson, K.A.; Boeynaems, J.M. P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov. Today, 2010, 15(13-14), 570-578.
[http://dx.doi.org/10.1016/j.drudis.2010.05.011] [PMID: 20594935]
[7]
Husted, S.; van Giezen, J.J.J. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc. Ther., 2009, 27(4), 259-274.
[http://dx.doi.org/10.1111/j.1755-5922.2009.00096.x] [PMID: 19604248]
[8]
Shi, S.T.; Herlihy, K.J.; Graham, J.P.; Nonomiya, J.; Rahavendran, S.V.; Skor, H.; Irvine, R.; Binford, S.; Tatlock, J.; Li, H.; Gonzalez, J.; Linton, A.; Patick, A.K.; Lewis, C. Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob. Agents Chemother., 2009, 53(6), 2544-2552.
[http://dx.doi.org/10.1128/AAC.01599-08] [PMID: 19307358]
[9]
Gentile, I.; Buonomo, A.R.; Zappulo, E.; Borgia, G. Discontinued drugs in 2012 - 2013: hepatitis C virus infection. Expert Opin. Investig. Drugs, 2015, 24(2), 239-251.
[http://dx.doi.org/10.1517/13543784.2015.982274] [PMID: 25384989]
[10]
Gomez, L.; Massari, M.E.; Vickers, T.; Freestone, G.; Vernier, W.; Ly, K.; Xu, R.; McCarrick, M.; Marrone, T.; Metz, M.; Yan, Y.G.; Yoder, Z.W.; Lemus, R.; Broadbent, N.J.; Barido, R.; Warren, N.; Schmelzer, K.; Neul, D.; Lee, D.; Andersen, C.B.; Sebring, K.; Aertgeerts, K.; Zhou, X.; Tabatabaei, A.; Peters, M.; Breitenbucher, J.G. Design and Synthesis of Novel and Selective Phosphodiesterase 2 (PDE2a) Inhibitors for the Treatment of Memory Disorders. J. Med. Chem., 2017, 60(5), 2037-2051.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01793] [PMID: 28165743]
[11]
Kumar, J.; Meena, P.; Singh, A.; Jameel, E.; Maqbool, M.; Mobashir, M.; Shandilya, A.; Tiwari, M.; Hoda, N.; Jayaram, B. Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer’s disease therapies. Eur. J. Med. Chem., 2016, 119, 260-277.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.053] [PMID: 27227482]
[12]
Kovalevich, J.; Cornec, A.S.; Yao, Y.; James, M.; Crowe, A.; Lee, V.M.Y.; Trojanowski, J.Q.; Smith, A.B., III; Ballatore, C.; Brunden, K.R. Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer’s Disease and Related Tauopathies. J. Pharmacol. Exp. Ther., 2016, 357(2), 432-450.
[http://dx.doi.org/10.1124/jpet.115.231175] [PMID: 26980057]
[13]
Cornec, A.S.; James, M.J.; Kovalevich, J.; Trojanowski, J.Q.; Lee, V.M.Y.; Smith, A.B., III; Ballatore, C.; Brunden, K.R. Pharmacokinetic, pharmacodynamic and metabolic characterization of a brain retentive microtubule (MT)-stabilizing triazolopyrimidine. Bioorg. Med. Chem. Lett., 2015, 25(21), 4980-4982.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.002] [PMID: 25819095]
[14]
Wang, S.; Zhao, L.J.; Zheng, Y.C.; Shen, D.D.; Miao, E.F.; Qiao, X.P.; Zhao, L.J.; Liu, Y.; Huang, R.; Yu, B.; Liu, H.M. Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors. Eur. J. Med. Chem., 2017, 125, 940-951.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.021] [PMID: 27769034]
[15]
Arenas-González, A.; Mendez-Delgado, L.A.; Merino-Montiel, P.; Padrón, J.M.; Montiel-Smith, S.; Vega-Báez, J.L.; Meza-Reyes, S. Synthesis of monomeric and dimeric steroids containing [1,2,4]triazolo[1,5-a]pyrimidines. Steroids, 2016, 116, 13-19.
[http://dx.doi.org/10.1016/j.steroids.2016.09.014] [PMID: 27692994]
[16]
Hassan, G.S.; El-Sherbeny, M.A.; El-Ashmawy, M.B.; Bayomi, S.M.; Maarouf, A.R.; Badria, F.A. Synthesis and Antitumor Testing of Certain New Fused Triazolopyrimidine and Triazoloquinazoline Derivatives. Arab. J. Chem., 2017, 10, 1345-1355.
[http://dx.doi.org/10.1016/j.arabjc.2013.04.002]
[17]
Jakubowski, M.; Łakomska, I.; Sitkowski, J.; Wiśniewska, J. Dicarboxylato Platinum(Ii) Complexes Containing Dimethyl Sulfoxide and Triazolopyrimidine as Potential Anticancer Agents: Synthesis, Structural and Biological Studies in Solution. New J. Chem., 2018, 42, 8113-8122.
[http://dx.doi.org/10.1039/C8NJ01199K]
[18]
Kokkonda, S.; Deng, X.; White, K.L.; Coteron, J.M.; Marco, M.; de Las Heras, L.; White, J.; El Mazouni, F.; Tomchick, D.R.; Manjalanagara, K.; Rudra, K.R.; Chen, G.; Morizzi, J.; Ryan, E.; Kaminsky, W.; Leroy, D.; Martínez-Martínez, M.S.; Jimenez-Diaz, M.B.; Bazaga, S.F.; Angulo-Barturen, I.; Waterson, D.; Burrows, J.N.; Matthews, D.; Charman, S.A.; Phillips, M.A.; Rathod, P.K. Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting Plasmodium falciparum Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity. J. Med. Chem., 2016, 59(11), 5416-5431.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00275] [PMID: 27127993]
[19]
Phillips, M.A.; White, K.L.; Kokkonda, S.; Deng, X.; White, J.; El Mazouni, F.; Marsh, K.; Tomchick, D.R.; Manjalanagara, K.; Rudra, K.R.; Wirjanata, G.; Noviyanti, R.; Price, R.N.; Marfurt, J.; Shackleford, D.M.; Chiu, F.C.K.; Campbell, M.; Jimenez-Diaz, M.B.; Bazaga, S.F.; Angulo-Barturen, I.; Martinez, M.S.; Lafuente-Monasterio, M.; Kaminsky, W.; Silue, K.; Zeeman, A.M.; Kocken, C.; Leroy, D.; Blasco, B.; Rossignol, E.; Rueckle, T.; Matthews, D.; Burrows, J.N.; Waterson, D.; Palmer, M.J.; Rathod, P.K.; Charman, S.A. a triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with improved drug-like properties for treatment and prevention of malaria. ACS Infect. Dis., 2016, 2(12), 945-957.
[http://dx.doi.org/10.1021/acsinfecdis.6b00144] [PMID: 27641613]
[20]
C S Pinheiro, L.; M Feitosa, L.; O Gandi, M.; F Silveira, F.; Boechat, N. The development of novel compounds against malaria: quinolines, triazolpyridines, pyrazolopyridines and pyrazolopyrimidines. Molecules, 2019, 24(22), 4095.
[http://dx.doi.org/10.3390/molecules24224095] [PMID: 31766184]
[21]
Jung, I.P.; Ha, N.R.; Lee, S.C.; Ryoo, S.W.; Yoon, M.Y. Development of potent chemical antituberculosis agents targeting Mycobacterium tuberculosis acetohydroxyacid synthase. Int. J. Antimicrob. Agents, 2016, 48(3), 247-258.
[http://dx.doi.org/10.1016/j.ijantimicag.2016.04.031] [PMID: 27451857]
[22]
Zuniga, E.S.; Korkegian, A.; Mullen, S.; Hembre, E.J.; Ornstein, P.L.; Cortez, G.; Biswas, K.; Kumar, N.; Cramer, J.; Masquelin, T.; Hipskind, P.A.; Odingo, J.; Parish, T. The synthesis and evaluation of triazolopyrimidines as anti-tubercular agents. Bioorg. Med. Chem., 2017, 25(15), 3922-3946.
[http://dx.doi.org/10.1016/j.bmc.2017.05.030] [PMID: 28576632]
[23]
Cai, D.; Zhang, Z.H.; Chen, Y.; Yan, X.J.; Zhang, S.T.; Zou, L.J.; Meng, L.H.; Li, F.; Fu, B.J. Synthesis of some new thiazolo[3,2-A]pyrimidine derivatives and screening of their in vitro antibacterial and antitubercular activities. Med. Chem. Res., 2016, 25, 292-302.
[http://dx.doi.org/10.1007/s00044-015-1481-y]
[24]
da Silva, E.R.; Boechat, N.; Pinheiro, L.C.S.; Bastos, M.M.; Costa, C.C.P.; Bartholomeu, J.C.; da Costa, T.H. Novel selective inhibitor of Leishmania (Leishmania) amazonensis arginase. Chem. Biol. Drug Des., 2015, 86(5), 969-978.
[http://dx.doi.org/10.1111/cbdd.12566] [PMID: 25845502]
[25]
Wang, H.; Lee, M.; Peng, Z.; Blázquez, B.; Lastochkin, E.; Kumarasiri, M.; Bouley, R.; Chang, M.; Mobashery, S. Synthesis and evaluation of 1,2,4-triazolo[1,5-a]pyrimidines as antibacterial agents against Enterococcus faecium. J. Med. Chem., 2015, 58(10), 4194-4203.
[http://dx.doi.org/10.1021/jm501831g] [PMID: 25923368]
[26]
Mohamed Ahmed, M.S.; Farghaly, T.A. Antimicrobial Activity of [1,2,4]Triazolo[4,3-a]Pyrimidine and New Pyrido[3,2-f][1,4]Thiazepine Derivatives. Lett. Org. Chem., 2018, 15, 183-190.
[http://dx.doi.org/10.2174/1570178614666171010161751]
[27]
Faizi, M.; Dabirian, S.; Tajali, H.; Ahmadi, F.; Zavareh, E.R.; Shahhosseini, S.; Tabatabai, S.A. Novel agonists of benzodiazepine receptors: design, synthesis, binding assay and pharmacological evaluation of 1,2,4-triazolo[1,5-a]pyrimidinone and 3-amino-1,2,4-triazole derivatives. Bioorg. Med. Chem., 2015, 23(3), 480-487.
[http://dx.doi.org/10.1016/j.bmc.2014.12.016] [PMID: 25564376]
[28]
Aghazadeh Tabrizi, M.; Baraldi, P.G.; Ruggiero, E.; Saponaro, G.; Baraldi, S.; Poli, G.; Tuccinardi, T.; Ravani, A.; Vincenzi, F.; Borea, P.A.; Varani, K. Synthesis and structure activity relationship investigation of triazolo[1,5-a]pyrimidines as CB2 cannabinoid receptor inverse agonists. Eur. J. Med. Chem., 2016, 113, 11-27.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.032] [PMID: 26922225]
[29]
Singh, P.K.; Choudhary, S.; Kashyap, A.; Verma, H.; Kapil, S.; Kumar, M.; Arora, M.; Silakari, O. An exhaustive compilation on chemistry of triazolopyrimidine: A journey through decades. Bioorg. Chem., 2019, 88, 102919.
[http://dx.doi.org/10.1016/j.bioorg.2019.102919] [PMID: 31026721]
[30]
El‐Sebaey, S.A. Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents. ChemistrySelect, 2020, 5, 11654-11680.
[http://dx.doi.org/10.1002/slct.202002830]
[31]
Oukoloff, K.; Lucero, B.; Francisco, K.R.; Brunden, K.R.; Ballatore, C. 1,2,4-Triazolo[1,5-a]pyrimidines in drug design. Eur. J. Med. Chem., 2019, 165, 332-346.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.027] [PMID: 30703745]
[32]
Revankar, G.R.; Robins, R.K.; Tolman, R.L. s-Triazolo(1,5-a)pyrimidine nucleosides. Site of N-glycosylation studies and the synthesis of an N-Bridgehead guanosine analog. J. Org. Chem., 1974, 39(9), 1256-1262.
[http://dx.doi.org/10.1021/jo00923a021] [PMID: 4833378]
[33]
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. Discovery of (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-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor. J. Med. Chem., 2009, 52(5), 1255-1258.
[http://dx.doi.org/10.1021/jm8014537] [PMID: 19209845]
[34]
Marwaha, A.; White, J.; El Mazouni, F.; Creason, S.A.; Kokkonda, S.; Buckner, F.S.; Charman, S.A.; Phillips, M.A.; Rathod, P.K. Bioisosteric transformations and permutations in the triazolopyrimidine scaffold to identify the minimum pharmacophore required for inhibitory activity against Plasmodium falciparum dihydroorotate dehydrogenase. J. Med. Chem., 2012, 55(17), 7425-7436.
[http://dx.doi.org/10.1021/jm300351w] [PMID: 22877245]
[35]
McCarthy, J.S.; Lotharius, J.; Rückle, T.; Chalon, S.; Phillips, M.A.; Elliott, S.; Sekuloski, S.; Griffin, P.; Ng, C.L.; Fidock, D.A.; Marquart, L.; Williams, N.S.; Gobeau, N.; Bebrevska, L.; Rosario, M.; Marsh, K.; Möhrle, J.J. Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study. Lancet Infect. Dis., 2017, 17(6), 626-635.
[http://dx.doi.org/10.1016/S1473-3099(17)30171-8] [PMID: 28363636]
[36]
Coteron, J.M.; Marco, M.; Esquivias, J.; Deng, X.; White, K.L.; White, J.; Koltun, M.; El Mazouni, F.; Kokkonda, S.; Katneni, K.; Bhamidipati, R.; Shackleford, D.M.; Angulo-Barturen, I.; Ferrer, S.B.; Jiménez-Díaz, M.B.; Gamo, F.J.; Goldsmith, E.J.; Charman, W.N.; Bathurst, I.; Floyd, D.; Matthews, D.; Burrows, J.N.; Rathod, P.K.; Charman, S.A.; Phillips, M.A. Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential. J. Med. Chem., 2011, 54(15), 5540-5561.
[http://dx.doi.org/10.1021/jm200592f] [PMID: 21696174]
[37]
Tresadern, G.; Velter, I.; Trabanco, A.A.; Van den Keybus, F.; Macdonald, G.J.; Somers, M.V.F.; Vanhoof, G.; Leonard, P.M.; Lamers, M.B.A.C.; Van Roosbroeck, Y.E.M.; Buijnsters, P.J.J.A. [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration. J. Med. Chem., 2020, 63(21), 12887-12910.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01272] [PMID: 33105987]
[38]
Wassermann, A.M.; Lounkine, E.; Hoepfner, D.; Le Goff, G.; King, F.J.; Studer, C.; Peltier, J.M.; Grippo, M.L.; Prindle, V.; Tao, J.; Schuffenhauer, A.; Wallace, I.M.; Chen, S.; Krastel, P.; Cobos-Correa, A.; Parker, C.N.; Davies, J.W.; Glick, M. Dark chemical matter as a promising starting point for drug lead discovery. Nat. Chem. Biol., 2015, 11(12), 958-966.
[http://dx.doi.org/10.1038/nchembio.1936] [PMID: 26479441]
[39]
Abu-Hashem, A.A.; Hussein, H.A.R.; Abu-zied, K.M. Synthesis of novel 1, 2, 4-triazolopyrimidines and their evaluation as antimicrobial AGENTS. Med. Chem. Res., 2017, 26, 120-130.
[http://dx.doi.org/10.1007/s00044-016-1733-5]
[40]
Ranjbar-Karimi, R.; Beiki-Shoraki, K.; Amiri, A. Three-component synthesis of some 2-amino-5-hydroxy-[1,2,4]triazolo[1,5-a] pyrimidine-6-carbonitriles and 2-(cyanoamino)-4-hydroxypyrimidine-5- carbonitriles. Monatsh. Chem., 2010, 141, 1101-1106.
[http://dx.doi.org/10.1007/s00706-010-0371-8]
[41]
Astakhov, A.V.; Zubatyuk, R.I.; Abagyan, R.S.; Chernyshev, V.M. Synthesis of [1,2,4]triazolo[4,3-a]pyrimidin-5(1h)-ones by the condensation of 3-alkylamino-5-amino-1-phenyl[1,2,4]triazoles with β-keto esters or diethyl ethoxymethylenemalonate. Chem. Heterocycl. Compd., 2014, 49, 1500-1507.
[http://dx.doi.org/10.1007/s10593-014-1401-y]
[42]
Massari, S.; Desantis, J.; Nannetti, G.; Sabatini, S.; Tortorella, S.; Goracci, L.; Cecchetti, V.; Loregian, A.; Tabarrini, O. Efficient and regioselective one-step synthesis of 7-aryl- 5-methyl- and 5-aryl-7-methyl-2-amino-[1,2,4]triazolo[1,5- a]pyrimidine derivatives. 2017.
[43]
Brown, D.J.; Nagamatsu, T. Isomerizations akin to the dimroth rearrangement. III. the conversion of simple s-triazolo[4,3-a]pyrimidines into their [1,5-a] isomers. Aust. J. Chem., 1977, 30, 2515-2525.
[http://dx.doi.org/10.1071/CH9772515]
[44]
Brown, D.J.; Nagamatsu, T. Isomerizations akin to the dimroth rearrangement. IV* formation of simple s-triazolo[l, 5-c]pyrimidines via their [4, 3-c] isomers. Aust. J. Chem., 1978, 31, 2505-2515.
[http://dx.doi.org/10.1071/CH9782505]
[45]
Roblin, R.O.; Lampen, J.O.; English, J.P.; Cole, Q.P.; Vaughan, J.R. Studies in chemotherapy. VIII. methionine and purine antagonists and their relation to the sulfonamides. J. Am. Chem. Soc., 1945, 67, 290-294.
[http://dx.doi.org/10.1021/ja01218a043]
[46]
Dille, K.L.; Christensen, B.E. Purines. III. the preparation of certain purine and triazolopyrimidine derivatives. J. Am. Chem. Soc., 1954, 76, 5087-5088.
[http://dx.doi.org/10.1021/ja01649a022]
[47]
Shealy, F.; Clayton, J.D.; O’Dell, A.; Montgomery, J.A. υ-triazolo[4,5-d]pyrimidines. II. o-substituted derivatives of 8-azaguanine and 8-azahypoxanthine. J. Org. Chem., 1962, 27, 4518-4523.
[http://dx.doi.org/10.1021/jo01059a096]
[48]
Kim, C.W.; Chang, K.M.; Hepatitis, C. Hepatitis C virus: virology and life cycle. Clin. Mol. Hepatol., 2013, 19(1), 17-25.
[http://dx.doi.org/10.3350/cmh.2013.19.1.17] [PMID: 23593605]
[49]
Geddawy, A.; Ibrahim, Y.F.; Elbahie, N.M.; Ibrahim, M.A. Direct Acting Anti-hepatitis C Virus Drugs: Clinical Pharmacology and Future Direction. J. Transl. Int. Med., 2017, 5(1), 8-17.
[http://dx.doi.org/10.1515/jtim-2017-0007] [PMID: 28680834]
[50]
Borgia, G.; Maraolo, A.E.; Nappa, S.; Gentile, I.; Buonomo, A.R. NS5B polymerase inhibitors in phase II clinical trials for HCV infection. Expert Opin. Investig. Drugs, 2018, 27(3), 243-250.
[http://dx.doi.org/10.1080/13543784.2018.1420780] [PMID: 29271672]
[51]
Gentile, I.; Maraolo, A.E.; Buonomo, A.R.; Zappulo, E.; Borgia, G. The discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C. Expert Opin. Drug Discov., 2015, 10(12), 1363-1377.
[http://dx.doi.org/10.1517/17460441.2015.1094051] [PMID: 26563720]
[52]
Li, H.; Linton, A.; Tatlock, J.; Gonzalez, J.; Borchardt, A.; Abreo, M.; Jewell, T.; Patel, L.; Drowns, M.; Ludlum, S.; Goble, M.; Yang, M.; Blazel, J.; Rahavendran, R.; Skor, H.; Shi, S.; Lewis, C.; Fuhrman, S. Allosteric inhibitors of hepatitis C polymerase: discovery of potent and orally bioavailable carbon-linked dihydropyrones. J. Med. Chem., 2007, 50(17), 3969-3972.
[http://dx.doi.org/10.1021/jm0704447] [PMID: 17658778]
[53]
Wagner, F.; Thompson, R.; Kantaridis, C.; Simpson, P.; Troke, P.J.F.; Jagannatha, S.; Neelakantan, S.; Purohit, V.S.; Hammond, J.L. Antiviral activity of the hepatitis C virus polymerase inhibitor filibuvir in genotype 1-infected patients. Hepatology, 2011, 54(1), 50-59.
[http://dx.doi.org/10.1002/hep.24342] [PMID: 21488067]
[54]
Rodriguez-Torres, M.; Yoshida, E.M.; Marcellin, P.; Srinivasan, S.; Purohit, V.S.; Wang, C.; Hammond, J.L. A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV. Ann. Hepatol., 2014, 13(4), 364-375.
[http://dx.doi.org/10.1016/S1665-2681(19)30843-9] [PMID: 24927607]
[55]
Pinior, B.; Firth, C.L.; Richter, V.; Lebl, K.; Trauffler, M.; Dzieciol, M.; Hutter, S.E.; Burgstaller, J.; Obritzhauser, W.; Winter, P.; Käsbohrer, A. A systematic review of financial and economic assessments of bovine viral diarrhea virus (BVDV) prevention and mitigation activities worldwide. Prev. Vet. Med., 2017, 137(Pt A), 77-92.
[http://dx.doi.org/10.1016/j.prevetmed.2016.12.014] [PMID: 28040270]
[56]
Baraldi, P.G.; Cacciari, B.; Spalluto, G. Pineda de las Infantas y Villatoro, M.J.; Zocchi, C.; Dionisotti, S.; Ongini, E. Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives: potent and selective A(2A) adenosine antagonists. J. Med. Chem., 1996, 39(5), 1164-1171.
[http://dx.doi.org/10.1021/jm950746l] [PMID: 8676354]
[57]
Paeshuyse, J.; Letellier, C.; Froeyen, M.; Dutartre, H.; Vrancken, R.; Canard, B.; De Clercq, E.; Gueiffier, A.; Teulade, J.C.; Herdewijn, P.; Puerstinger, G.; Koenen, F.; Kerkhofs, P.; Baraldi, P.G.; Neyts, J. A pyrazolotriazolopyrimidinamine inhibitor of bovine viral diarrhea virus replication that targets the viral RNA-dependent RNA polymerase. Antiviral Res., 2009, 82(3), 141-147.
[http://dx.doi.org/10.1016/j.antiviral.2009.02.192] [PMID: 19428605]
[58]
Choi, K.H.; Groarke, J.M.; Young, D.C.; Kuhn, R.J.; Smith, J.L.; Pevear, D.C.; Rossmann, M.G. The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4425-4430.
[http://dx.doi.org/10.1073/pnas.0400660101] [PMID: 15070734]
[59]
Ten threats to global health in 2019. Available from: https://www.who.int/emergencies/ten-threats-to-global-health-in-2019 (accessed Apr 7, 2019)
[60]
Diamond, M.S.; Pierson, T.C. Molecular Insight into Dengue Virus Pathogenesis and Its Implications for Disease Control. Cell, 2015, 162(3), 488-492.
[http://dx.doi.org/10.1016/j.cell.2015.07.005] [PMID: 26232221]
[61]
Wilder-Smith, A.; Gubler, D.J.; Weaver, S.C.; Monath, T.P.; Heymann, D.L.; Scott, T.W. Epidemic arboviral diseases: priorities for research and public health. Lancet Infect. Dis., 2017, 17(3), e101-e106.
[http://dx.doi.org/10.1016/S1473-3099(16)30518-7] [PMID: 28011234]
[62]
Lim, S.P. Dengue drug discovery: Progress, challenges and outlook. Antiviral Res., 2019, 163, 156-178.
[http://dx.doi.org/10.1016/j.antiviral.2018.12.016] [PMID: 30597183]
[63]
Felicetti, T.; Manfroni, G.; Cecchetti, V.; Cannalire, R. Broad‐spectrum flavivirus inhibitors: a medicinal chemistry point of view. ChemMedChem, 2020. cmdc.202000464
[http://dx.doi.org/10.1002/cmdc.202000464]
[64]
Lim, S.P.; Noble, C.G.; Seh, C.C.; Soh, T.S.; El Sahili, A.; Chan, G.K.Y.; Lescar, J.; Arora, R.; Benson, T.; Nilar, S.; Manjunatha, U.; Wan, K.F.; Dong, H.; Xie, X.; Shi, P-Y.; Yokokawa, F. Potent Allosteric Dengue Virus NS5 Polymerase Inhibitors: Mechanism of Action and Resistance Profiling. PLoS Pathog., 2016, 12(8), e1005737.
[http://dx.doi.org/10.1371/journal.ppat.1005737] [PMID: 27500641]
[65]
Wan, Y. hong; Wu, W. yu; Guo, S. xin; He, S. jun; Tang, X. dong; Wu, X. yun; Nandakumar, K. S.; Zou, M.; Li, L.; Chen, X. guang; Liu, S. wen; Yao, X. gang. [1,2,4]Triazolo[1,5-a]Pyrimidine Derivative (Mol-5) Is a New NS5-RdRp Inhibitor of DENV2 Proliferation and DENV2-Induced Inflammation. Acta Pharmacol. Sin., 2020, 41, 706-718.
[http://dx.doi.org/10.1038/s41401-019-0316-7] [PMID: 31729469]
[66]
Kendall, C.; Khalid, H.; Müller, M.; Banda, D.H.; Kohl, A.; Merits, A.; Stonehouse, N.J.; Tuplin, A. Structural and phenotypic analysis of Chikungunya virus RNA replication elements. Nucleic Acids Res., 2019, 47(17), 9296-9312.
[http://dx.doi.org/10.1093/nar/gkz640] [PMID: 31350895]
[67]
Symptoms, Diagnosis, & Treatment | Chikungunya virus | CDC. Available from: https://www.cdc.gov/chikungunya/symptoms/index.html (ac cessed Sep 20, 2020)
[68]
Gigante, A.; Canela, M.D.; Delang, L.; Priego, E.M.; Camarasa, M.J.; Querat, G.; Neyts, J.; Leyssen, P.; Pérez-Pérez, M.J. Identification of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as novel inhibitors of Chikungunya virus replication. J. Med. Chem., 2014, 57(10), 4000-4008.
[http://dx.doi.org/10.1021/jm401844c] [PMID: 24800626]
[69]
Delang, L.; Li, C.; Tas, A.; Quérat, G.; Albulescu, I.C.; De Burghgraeve, T.; Guerrero, N.A.; Gigante, A.; Piorkowski, G.; Decroly, E.; Jochmans, D.; Canard, B.; Snijder, E.J.; Pérez-Pérez, M.J.; van Hemert, M.J.; Coutard, B.; Leyssen, P.; Neyts, J. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection. Sci. Rep., 2016, 6, 31819.
[http://dx.doi.org/10.1038/srep31819] [PMID: 27545976]
[70]
Gigante, A.; Gómez-SanJuan, A.; Delang, L.; Li, C.; Bueno, O.; Gamo, A.M.; Priego, E.M.; Camarasa, M.J.; Jochmans, D.; Leyssen, P.; Decroly, E.; Coutard, B.; Querat, G.; Neyts, J.; Pérez-Pérez, M.J. Antiviral activity of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones against chikungunya virus targeting the viral capping nsP1. Antiviral Res., 2017, 144, 216-222.
[http://dx.doi.org/10.1016/j.antiviral.2017.06.003] [PMID: 28619679]
[71]
Gómez-SanJuan, A.; Gamo, A.M.; Delang, L.; Pérez-Sánchez, A.; Amrun, S.N.; Abdelnabi, R.; Jacobs, S.; Priego, E.M.; Camarasa, M.J.; Jochmans, D.; Leyssen, P.; Ng, L.F.P.; Querat, G.; Neyts, J.; Pérez-Pérez, M.J. Inhibition of the Replication of Different Strains of Chikungunya Virus by 3-Aryl-[1,2,3]triazolo[4,5- d]pyrimidin-7(6 H)-ones. ACS Infect. Dis., 2018, 4(4), 605-619.
[http://dx.doi.org/10.1021/acsinfecdis.7b00219] [PMID: 29406692]
[72]
Toots, M.; Plemper, R.K. Next-generation direct-acting influenza therapeutics. Transl. Res., 2020, 220, 33-42.
[http://dx.doi.org/10.1016/j.trsl.2020.01.005] [PMID: 32088166]
[73]
Mifsud, E.J.; Hayden, F.G.; Hurt, A.C. Antivirals targeting the polymerase complex of influenza viruses. Antiviral Res., 2019, 169, 104545.
[http://dx.doi.org/10.1016/j.antiviral.2019.104545] [PMID: 31247246]
[74]
Zhang, J.; Hu, Y.; Musharrafieh, R.; Yin, H.; Wang, J. Focusing on the influenza virus polymerase complex: recent progress in drug discovery and assay development. Curr. Med. Chem., 2019, 26(13), 2243-2263.
[http://dx.doi.org/10.2174/0929867325666180706112940] [PMID: 29984646]
[75]
Giacchello, I.; Musumeci, F.; D’Agostino, I.; Greco, C.; Grossi, G.; Schenone, S. Insights into RNA-dependent RNA polymerase inhibitors as anti-influenza virus agents. Curr. Med. Chem., 2020, 27.
[http://dx.doi.org/10.2174/0929867327666200114115632]
[76]
Fodor, E.; Te Velthuis, A.J.W. Structure And Function Of The Influenza Virus Transcription And Replication Machinery. Cold Spring Harb. Perspect. Med., 2020, 10(9), a038398.
[http://dx.doi.org/10.1101/cshperspect.a038398] [PMID: 31871230]
[77]
Wandzik, J.M.; Kouba, T.; Cusack, S. Structure and function of influenza polymerase. Cold Spring Harb. Perspect. Med., 2020, a038372.
[http://dx.doi.org/10.1101/cshperspect.a038372] [PMID: 32341065]
[78]
Furuta, Y.; Takahashi, K.; Fukuda, Y.; Kuno, M.; Kamiyama, T.; Kozaki, K.; Nomura, N.; Egawa, H.; Minami, S.; Watanabe, Y.; Narita, H.; Shiraki, K. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob. Agents Chemother., 2002, 46(4), 977-981.
[http://dx.doi.org/10.1128/AAC.46.4.977-981.2002] [PMID: 11897578]
[79]
Furuta, Y.; Gowen, B.B.; Takahashi, K.; Shiraki, K.; Smee, D.F.; Barnard, D.L. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res., 2013, 100(2), 446-454.
[http://dx.doi.org/10.1016/j.antiviral.2013.09.015] [PMID: 24084488]
[80]
Jones, J.C.; Marathe, B.M.; Lerner, C.; Kreis, L.; Gasser, R.; Pascua, P.N.Q.; Najera, I.; Govorkova, E.A. A novel endonuclease inhibitor exhibits broad-spectrum anti-influenza virus activity in vitro. Antimicrob. Agents Chemother., 2016, 60(9), 5504-5514.
[http://dx.doi.org/10.1128/AAC.00888-16] [PMID: 27381402]
[81]
Noshi, T.; Kitano, M.; Taniguchi, K.; Yamamoto, A.; Omoto, S.; Baba, K.; Hashimoto, T.; Ishida, K.; Kushima, Y.; Hattori, K.; Kawai, M.; Yoshida, R.; Kobayashi, M.; Yoshinaga, T.; Sato, A.; Okamatsu, M.; Sakoda, Y.; Kida, H.; Shishido, T.; Naito, A. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res., 2018, 160, 109-117.
[http://dx.doi.org/10.1016/j.antiviral.2018.10.008] [PMID: 30316915]
[82]
Clark, M.P.; Ledeboer, M.W.; Davies, I.; Byrn, R.A.; Jones, S.M.; Perola, E.; Tsai, A.; Jacobs, M.; Nti-Addae, K.; Bandarage, U.K.; Boyd, M.J.; Bethiel, R.S.; Court, J.J.; Deng, H.; Duffy, J.P.; Dorsch, W.A.; Farmer, L.J.; Gao, H.; Gu, W.; Jackson, K.; Jacobs, D.H.; Kennedy, J.M.; Ledford, B.; Liang, J.; Maltais, F.; Murcko, M.; Wang, T.; Wannamaker, M.W.; Bennett, H.B.; Leeman, J.R.; McNeil, C.; Taylor, W.P.; Memmott, C.; Jiang, M.; Rijnbrand, R.; Bral, C.; Germann, U.; Nezami, A.; Zhang, Y.; Salituro, F.G.; Bennani, Y.L.; Charifson, P.S. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J. Med. Chem., 2014, 57(15), 6668-6678.
[http://dx.doi.org/10.1021/jm5007275] [PMID: 25019388]
[83]
Massari, S.; Goracci, L.; Desantis, J.; Tabarrini, O. Polymerase acidic protein-basic protein 1 (PA-PB1) protein-protein interaction as a target for next-generation anti-influenza therapeutics. J. Med. Chem., 2016, 59(17), 7699-7718.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01474] [PMID: 27046062]
[84]
Massari, S.; Desantis, J.; Nizi, M. G.; Cecchetti, V.; Tabarrini, O. Inhibition of influenza virus polymerase by interfering with its protein-protein interactions. ACS Infect. Dis., 2020. acsinfecdis.0c00552.
[85]
He, X.; Zhou, J.; Bartlam, M.; Zhang, R.; Ma, J.; Lou, Z.; Li, X.; Li, J.; Joachimiak, A.; Zeng, Z.; Ge, R.; Rao, Z.; Liu, Y. Crystal structure of the polymerase PA(C)-PB1(N) complex from an avian influenza H5N1 virus. Nature, 2008, 454(7208), 1123-1126.
[http://dx.doi.org/10.1038/nature07120] [PMID: 18615018]
[86]
Muratore, G.; Goracci, L.; Mercorelli, B.; Foeglein, Á.; Digard, P.; Cruciani, G.; Palù, G.; Loregian, A. Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase. Proc. Natl. Acad. Sci. USA, 2012, 109(16), 6247-6252.
[http://dx.doi.org/10.1073/pnas.1119817109] [PMID: 22474359]
[87]
Lepri, S.; Nannetti, G.; Muratore, G.; Cruciani, G.; Ruzziconi, R.; Mercorelli, B.; Palù, G.; Loregian, A.; Goracci, L. Optimization of small-molecule inhibitors of influenza virus polymerase: from thiophene-3-carboxamide to polyamido scaffolds. J. Med. Chem., 2014, 57(10), 4337-4350.
[http://dx.doi.org/10.1021/jm500300r] [PMID: 24785979]
[88]
Massari, S.; Nannetti, G.; Desantis, J.; Muratore, G.; Sabatini, S.; Manfroni, G.; Mercorelli, B.; Cecchetti, V.; Palù, G.; Cruciani, G.; Loregian, A.; Goracci, L.; Tabarrini, O. A Broad anti-influenza hybrid small molecule that potently disrupts the interaction of polymerase acidic protein-basic protein 1 (PA-PB1) subunits. J. Med. Chem., 2015, 58(9), 3830-3842.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00012] [PMID: 25856229]
[89]
Liu, H.; Yao, X. Molecular basis of the interaction for an essential subunit PA-PB1 in influenza virus RNA polymerase: insights from molecular dynamics simulation and free energy calculation. Mol. Pharm., 2010, 7(1), 75-85.
[http://dx.doi.org/10.1021/mp900131p] [PMID: 19883112]
[90]
Massari, S.; Bertagnin, C.; Pismataro, M.C.; Donnadio, A.; Nannetti, G.; Felicetti, T.; Di Bona, S.; Nizi, M.G.; Tensi, L.; Manfroni, G.; Loza, M.I.; Sabatini, S.; Cecchetti, V.; Brea, J.; Goracci, L.; Loregian, A.; Tabarrini, O. Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase. Eur. J. Med. Chem., 2021, 209, 112944.
[http://dx.doi.org/10.1016/j.ejmech.2020.112944] [PMID: 33328103]
[91]
Yuan, S.; Chu, H.; Zhao, H.; Zhang, K.; Singh, K.; Chow, B.K.C.; Kao, R.Y.T.; Zhou, J.; Zheng, B-J. Identification of a small-molecule inhibitor of influenza virus via disrupting the subunits interaction of the viral polymerase. Antiviral Res., 2016, 125, 34-42.
[http://dx.doi.org/10.1016/j.antiviral.2015.11.005] [PMID: 26593979]
[92]
Lucas, S.; Nelson, A.M. HIV and the spectrum of human disease. J. Pathol., 2015, 235(2), 229-241.
[http://dx.doi.org/10.1002/path.4449] [PMID: 25251832]
[93]
Yu, F.; Pang, R.; Yuan, D.; He, M.; Zhang, C.; Chen, S.; Yang, M. Design, Synthesis, and Biological Evaluation of Novel Substituted [1,2,3] Triazolo[4,5-d]Pyrimidines as HIV-1 Tat-TAR Interaction Inhibitors. 2010, 82, 339-347.
[94]
Massari, S.; Sabatini, S.; Tabarrini, O. Blocking HIV-1 replication by targeting the Tat-hijacked transcriptional machinery. Curr. Pharm. Des., 2013, 19(10), 1860-1879.
[http://dx.doi.org/10.2174/1381612811319100010] [PMID: 23092279]
[95]
Tabarrini, O.; Desantis, J.; Massari, S. Recent advances in the identification of Tat-mediated transactivation inhibitors: progressing toward a functional cure of HIV. Future Med. Chem., 2016, 8(4), 421-442.
[http://dx.doi.org/10.4155/fmc.16.3] [PMID: 26933891]
[96]
Tabarrini, O.; Massari, S.; Cecchetti, V. 6-desfluoroquinolones as HIV-1 Tat-mediated transcription inhibitors. Future Med. Chem., 2010, 2(7), 1161-1180.
[http://dx.doi.org/10.4155/fmc.10.208] [PMID: 21426162]
[97]
Wang, L.; Tian, Y.; Chen, W.; Liu, H.; Zhan, P.; Li, D.; Liu, H.; De Clercq, E.; Pannecouque, C.; Liu, X. Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach. Eur. J. Med. Chem., 2014, 85, 293-303.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.104] [PMID: 25089812]
[98]
Li, D.; Zhan, P.; De Clercq, E.; Liu, X. Strategies for the design of HIV-1 non-nucleoside reverse transcriptase inhibitors: lessons from the development of seven representative paradigms. J. Med. Chem., 2012, 55(8), 3595-3613.
[http://dx.doi.org/10.1021/jm200990c] [PMID: 22268494]
[99]
Raney, A.; Hamatake, R.; Xu, W. RDEA427 and RDEA640 Are Novel NNRTI with Potent Anti-HIV Activity against NNRTI-Resistant Viruses. 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA 2008.
[100]
Dalvie, D.; Kang, P.; Loi, C-M.; Goulet, L.; Nair, S. Chapter 7: Influence of Heteroaromatic Rings on ADME Properties of Drugs. In: RSC Drug Discovery Series;; , 2010. Vol. 1, pp. 328-369.
[101]
Lansdon, E.B.; Brendza, K.M.; Hung, M.; Wang, R.; Mukund, S.; Jin, D.; Birkus, G.; Kutty, N.; Liu, X. Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design. J. Med. Chem., 2010, 53(10), 4295-4299.
[http://dx.doi.org/10.1021/jm1002233] [PMID: 20438081]
[102]
Huang, B.; Li, C.; Chen, W.; Liu, T.; Yu, M.; Fu, L.; Sun, Y.; Liu, H.; De Clercq, E.; Pannecouque, C.; Balzarini, J.; Zhan, P.; Liu, X. Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches. Eur. J. Med. Chem., 2015, 92, 754-765.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.042] [PMID: 25626145]
[103]
Song, Y.; Chen, W.; Kang, D.; Zhang, Q.; Zhan, P.; Liu, X. “Old friends in new guise”: exploiting privileged structures for scaffold re-evolution/refining. Comb. Chem. High Throughput Screen., 2014, 17(6), 536-553.
[http://dx.doi.org/10.2174/1386207317666140122101631] [PMID: 24446784]
[104]
Kertesz, D.J.; Brotherton-Pleiss, C.; Yang, M.; Wang, Z.; Lin, X.; Qiu, Z.; Hirschfeld, D.R.; Gleason, S.; Mirzadegan, T.; Dunten, P.W.; Harris, S.F.; Villaseñor, A.G.; Hang, J.Q.; Heilek, G.M.; Klumpp, K. Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses. Bioorg. Med. Chem. Lett., 2010, 20(14), 4215-4218.
[http://dx.doi.org/10.1016/j.bmcl.2010.05.040] [PMID: 20538456]
[105]
Desantis, J.; Massari, S.; Corona, A.; Astolfi, A.; Sabatini, S.; Manfroni, G.; Palazzotti, D.; Cecchetti, V.; Pannecouque, C.; Tramontano, E.; Tabarrini, O. 1,2,4-triazolo[1,5-a]pyrimidines as a novel class of inhibitors of the HIV-1 reverse transcriptase-associated ribonuclease H activity. Molecules, 2020, 25(5), 1183.
[http://dx.doi.org/10.3390/molecules25051183] [PMID: 32151066]
[106]
Sarafianos, S.G.; Marchand, B.; Das, K.; Himmel, D.M.; Parniak, M.A.; Hughes, S.H.; Arnold, E. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J. Mol. Biol., 2009, 385(3), 693-713.
[http://dx.doi.org/10.1016/j.jmb.2008.10.071] [PMID: 19022262]
[107]
Corona, A.; Masaoka, T.; Tocco, G.; Tramontano, E.; Le Grice, S.F. Active site and allosteric inhibitors of the ribonuclease H activity of HIV reverse transcriptase. Future Med. Chem., 2013, 5(18), 2127-2139.
[http://dx.doi.org/10.4155/fmc.13.178] [PMID: 24261890]
[108]
Su, H-P.; Yan, Y.; Prasad, G.S.; Smith, R.F.; Daniels, C.L.; Abeywickrema, P.D.; Reid, J.C.; Loughran, H.M.; Kornienko, M.; Sharma, S.; Grobler, J.A.; Xu, B.; Sardana, V.; Allison, T.J.; Williams, P.D.; Darke, P.L.; Hazuda, D.J.; Munshi, S. Structural basis for the inhibition of RNase H activity of HIV-1 reverse transcriptase by RNase H active site-directed inhibitors. J. Virol., 2010, 84(15), 7625-7633.
[http://dx.doi.org/10.1128/JVI.00353-10] [PMID: 20484498]
[109]
Parrish, J.; Tong, L.; Wang, M.; Chen, X.; Lansdon, E.B.; Cannizzaro, C.; Zheng, X.; Desai, M.C.; Xu, L. Synthesis and biological evaluation of phosphonate analogues of nevirapine. Bioorg. Med. Chem. Lett., 2013, 23(5), 1493-1497.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.049] [PMID: 23375792]
[110]
Lugo, D.; Krogstad, P. Enteroviruses in the early 21st century: new manifestations and challenges. Curr. Opin. Pediatr., 2016, 28(1), 107-113.
[http://dx.doi.org/10.1097/MOP.0000000000000303] [PMID: 26709690]
[111]
Suresh, S.; Rawlinson, W.D.; Andrews, P.I.; Stelzer-Braid, S. Global epidemiology of nonpolio enteroviruses causing severe neurological complications: A systematic review and meta-analysis. Rev. Med. Virol., 2020, 30(1), e2082.
[http://dx.doi.org/10.1002/rmv.2082] [PMID: 31588651]
[112]
Kumar Biswas, B.; Malpani, Y.R.; Ha, N.; Kwon, D.H.; Soo Shin, J.; Kim, H.S.; Kim, C.; Bong Han, S.; Lee, C.K.; Jung, Y.S. Enterovirus inhibitory activity of C-8-tert-butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones. Bioorg. Med. Chem. Lett., 2017, 27(15), 3582-3585.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.030] [PMID: 28587824]
[113]
Pierra Rouviere, C.; Dousson, C.B.; Tavis, J.E. HBV Replication Inhibitors.Antiviral Research; Elsevier B.V., 2020.
[114]
Yu, W.; Goddard, C.; Clearfield, E.; Mills, C.; Xiao, T.; Guo, H.; Morrey, J.D.; Motter, N.E.; Zhao, K.; Block, T.M.; Cuconati, A.; Xu, X. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J. Med. Chem., 2011, 54(16), 5660-5670.
[http://dx.doi.org/10.1021/jm200696v] [PMID: 21786803]
[115]
Heermann, K.H.; Goldmann, U.; Schwartz, W.; Seyffarth, T.; Baumgarten, H.; Gerlich, W.H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J. Virol., 1984, 52(2), 396-402.
[http://dx.doi.org/10.1128/JVI.52.2.396-402.1984] [PMID: 6492255]
[116]
Xu, Y.; Hu, Y.; Shi, B.; Zhang, X.; Wang, J.; Zhang, Z.; Shen, F.; Zhang, Q.; Sun, S.; Yuan, Z. HBsAg inhibits TLR9-mediated activation and IFN-α production in plasmacytoid dendritic cells. Mol. Immunol., 2009, 46(13), 2640-2646.
[http://dx.doi.org/10.1016/j.molimm.2009.04.031] [PMID: 19501403]
[117]
Dougherty, A.M.; Guo, H.; Westby, G.; Liu, Y.; Simsek, E.; Guo, J.T.; Mehta, A.; Norton, P.; Gu, B.; Block, T.; Cuconati, A. A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion. Antimicrob. Agents Chemother., 2007, 51(12), 4427-4437.
[http://dx.doi.org/10.1128/AAC.00541-07] [PMID: 17875990]
[118]
Kimberlin, D.W.; Whitley, R.J. Antiviral Therapy of HSV-1 and-2.Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis; Cambridge University Press, 2007, pp. 1153-1174.
[http://dx.doi.org/10.1017/CBO9780511545313.065]
[119]
Deev, S.L.; Yasko, M.V.; Karpenko, I.L.; Korovina, A.N.; Khandazhinskaya, A.L.; Andronova, V.L.; Galegov, G.A.; Shestakova, T.S.; Ulomskii, E.N.; Rusinov, V.L.; Chupakhin, O.N.; Kukhanova, M.K. 1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors. Bioorg. Chem., 2010, 38(6), 265-270.
[http://dx.doi.org/10.1016/j.bioorg.2010.09.002] [PMID: 20947122]
[120]
Goma’a, H.M.; Ghaly, M.A.; Abou‐zeid, L.A.; Badria, F.A.; Shehata, I.A.; El‐Kerdawy, M.M. Synthesis, biological evaluation and in silico studies of 1,2,4‐triazole and 1,3,4‐thiadiazole derivatives as antiherpetic agents. ChemistrySelect, 2019, 4, 6421-6428.
[http://dx.doi.org/10.1002/slct.201900814]
[121]
Bennett, M.S.; Wien, F.; Champness, J.N.; Batuwangala, T.; Rutherford, T.; Summers, W.C.; Sun, H.; Wright, G.; Sanderson, M.R. Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir. FEBS Lett., 1999, 443(2), 121-125.
[http://dx.doi.org/10.1016/S0014-5793(98)01619-6] [PMID: 9989588]

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