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Mini-Reviews in Medicinal Chemistry

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ISSN (Online): 1875-5607

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Mini-Review Article

Antiviral Activity of Pyrimidine Containing Compounds: Patent Review

Author(s): Thoraya A. Farghaly*, Marwa F. Harras, Amani M.R. Alsaedi, Halima A. Thakir, Huda K. Mahmoud and Dina F. Katowah

Volume 23, Issue 7, 2023

Published on: 06 January, 2023

Page: [821 - 851] Pages: 31

DOI: 10.2174/1389557523666221220142911

Price: $65

Abstract

Viruses are still the most prevalent infectious pathogens on a worldwide scale, with many of them causing life-threatening illnesses in humans. Influenza viruses, because of their significant morbidity and mortality, continue to pose a major threat to human health. According to WHO statistics, seasonal influenza virus epidemics are predicted to cause over 2 million severe illness cases with high death rates yearly. The whole world has been suffering from the COVID-19 epidemic for two years and is still suffering so far, and the deaths from this virus have exceeded three million cases. Because the great majority of viral infections do not have a specific medication or vaccination, discovering novel medicines remains a vital task. This review covers reports in the patent literature from 1980 to the end of 2021 on the antiviral activities of pyrimidine moieties. The patent database, SciFinder, was used to locate patent applications. A large variety of pyrimidine molecules have been produced and tested for antiviral activity over the last decade. These molecules were reported to inhibit a wide range of viruses, including influenza virus, respiratory syncytial virus, rhinovirus, dengue virus, herpes virus, hepatitis B and C, and human immunodeficiency virus. The cytotoxicity of the developed pyrimidine derivatives was tested in almost all reported studies and the selectivity index was calculated to show the selectivity and safety of such molecules. From the remarkable activity of pyrimidine compounds as antivirals for several dangerous viruses, we expect that these derivatives will be used as potent drugs in the very near future.

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[1]
Chung, D.H.; Golden, J.E.; Adcock, R.S.; Schroeder, C.E.; Chu, Y.K.; Sotsky, J.B.; Cramer, D.E.; Chilton, P.M.; Song, C.; Anantpadma, M.; Davey, R.A.; Prodhan, A.I.; Yin, X.; Zhang, X. Discovery of a broad-spectrum antiviral compound that inhibits pyrimidine biosynthesis and establishes a type 1 interferon-independent antiviral state. Antimicrob. Agents Chemother., 2016, 60(8), 4552-4562.
[http://dx.doi.org/10.1128/AAC.00282-16] [PMID: 27185801]
[2]
Mermer, A.; Keles, T.; Sirin, Y. Recent studies of nitrogen containing heterocyclic compounds as novel antiviral agents: A review. Bioorg. Chem., 2021, 114, 105076.
[http://dx.doi.org/10.1016/j.bioorg.2021.105076] [PMID: 34157555]
[3]
Wu, C.; Liu, Y.; Yang, Y.; Zhang, P.; Zhong, W.; Wang, Y.; Wang, Q.; Xu, Y.; Li, M.; Li, X.; Zheng, M.; Chen, L.; Li, H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B, 2020, 10(5), 766-788.
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[4]
Corman, V.M. Hosts and sources of endemic human coronaviruses. In: Advances in virus research; Elsevier, 2018; pp. 163-188.
[5]
Debing, Y.; Jochmans, D.; Neyts, J. Intervention strategies for emerging viruses: use of antivirals. Curr. Opin. Virol., 2013, 3(2), 217-224.
[http://dx.doi.org/10.1016/j.coviro.2013.03.001] [PMID: 23562753]
[6]
Xiao, M.; Xu, L.; Lin, D.; Lian, W.; Cui, M.; Zhang, M.; Yan, X.; Li, S.; Zhao, J.; Ye, J.; Liu, A.; Hu, A. Design, synthesis, and bioassay of 4-thiazolinone derivatives as influenza neuraminidase inhibitors. Eur. J. Med. Chem., 2021, 213, 113161.
[http://dx.doi.org/10.1016/j.ejmech.2021.113161] [PMID: 33540229]
[7]
Mitrasinovic, P. Advances in the structure-based design of the influenza A neuraminidase inhibitors. Curr. Drug Targets, 2010, 11(3), 315-326.
[http://dx.doi.org/10.2174/138945010790711932] [PMID: 20210756]
[8]
Schwerdtfeger, S.M.; Melzig, M.F. Sialidases in biological systems. Pharmazie, 2010, 65(8), 551-561.
[PMID: 20824954]
[9]
Cox, R.M.; Toots, M.; Yoon, J.J.; Sourimant, J.; Ludeke, B.; Fearns, R.; Bourque, E.; Patti, J.; Lee, E.; Vernachio, J.; Plemper, R.K. Development of an allosteric inhibitor class blocking RNA elongation by the respiratory syncytial virus polymerase complex. J. Biol. Chem., 2018, 293(43), 16761-16777.
[http://dx.doi.org/10.1074/jbc.RA118.004862] [PMID: 30206124]
[10]
Shi, W.; Jiang, Z.; He, H.; Xiao, F.; Lin, F.; Sun, Y.; Hou, L.; Shen, L.; Han, L.; Zeng, M.; Lai, K.; Gu, Z.; Chen, X.; Zhao, T.; Guo, L.; Yang, C.; Li, J.; Chen, S. Discovery of 3,3′-Spiro[Azetidine]-2-oxo-indoline derivatives as fusion inhibitors for treatment of RSV infection. ACS Med. Chem. Lett., 2018, 9(2), 94-97.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00418] [PMID: 29456794]
[11]
You, C.R.; Lee, S.W.; Jang, J.W.; Yoon, S.K. Update on hepatitis B virus infection. World J. Gastroenterol., 2014, 20(37), 13293-13305.
[http://dx.doi.org/10.3748/wjg.v20.i37.13293] [PMID: 25309066]
[12]
Gower, E.; Estes, C.; Blach, S.; Razavi-Shearer, K.; Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J. Hepatol., 2014, 61(S1), S45-S57.
[http://dx.doi.org/10.1016/j.jhep.2014.07.027] [PMID: 25086286]
[13]
Powdrill, M.H.; Deval, J.; Narjes, F.; De Francesco, R.; Götte, M. Mechanism of hepatitis C virus RNA polymerase inhibition with dihydroxypyrimidines. Antimicrob. Agents Chemother., 2010, 54(3), 977-983.
[http://dx.doi.org/10.1128/AAC.01216-09] [PMID: 20028820]
[14]
Koch, U.; Attenni, B.; Malancona, S.; Colarusso, S.; Conte, I.; Di Filippo, M.; Harper, S.; Pacini, B.; Giomini, C.; Thomas, S.; Incitti, I.; Tomei, L.; De Francesco, R.; Altamura, S.; Matassa, V.G.; Narjes, F. 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis. J. Med. Chem., 2006, 49(5), 1693-1705.
[http://dx.doi.org/10.1021/jm051064t] [PMID: 16509585]
[15]
Summa, V.; Petrocchi, A.; Pace, P.; Matassa, V.G.; De Francesco, R.; Altamura, S.; Tomei, L.; Koch, U.; Neuner, P. Discovery of alpha,gamma-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. J. Med. Chem., 2004, 47(1), 14-17.
[http://dx.doi.org/10.1021/jm0342109] [PMID: 14695815]
[16]
Xiao, T.; Tang, J.F.; Meng, G.; Pannecouque, C.; Zhu, Y.Y.; Liu, G.Y.; Xu, Z.Q.; Wu, F.S.; Gu, S.X.; Chen, F.E. Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities. Eur. J. Med. Chem., 2020, 186, 111864.
[http://dx.doi.org/10.1016/j.ejmech.2019.111864]
[17]
Curreli, F.; Ahmed, S.; Benedict Victor, S.M.; Iusupov, I.R.; Belov, D.S.; Markov, P.O.; Kurkin, A.V.; Altieri, A.; Debnath, A.K. Preclinical optimization of gp120 entry-antagonists as anti- HIV-1 agents with improved cytotoxicity and ADME properties through rational design, synthesis, and antiviral evaluation. J. Med. Chem., 2020, 63(4), 1724-1749.
[http://dx.doi.org/10.1021/acs.jmedchem.9b02149] [PMID: 32031803]
[18]
Cannalire, R.; Ki Chan, K.W.; Burali, M.S.; Gwee, C.P.; Wang, S.; Astolfi, A.; Massari, S.; Sabatini, S.; Tabarrini, O.; Mastrangelo, E.; Barreca, M.L.; Cecchetti, V.; Vasudevan, S.G.; Manfroni, G. Pyridobenzothiazolones exert potent anti-dengue activity by hampering multiple functions of NS5 polymerase. ACS Med. Chem. Lett., 2020, 11(5), 773-782.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00619] [PMID: 32435384]
[19]
Yasmin, F.; Yaqub, T.; Khan, I.; Shahzad, W.; Abu Saeed, H.; Tahir, Z.; Mukhtar, N.; Umar, S. Antiviral activity of thiazolide derivatives against dengue virus in Huh-7 cell line J. Microbiol., 2018, 11(2), e62467/1-e62467/6.
[20]
Arankalle, V.A.; Shrivastava, S.; Cherian, S.; Gunjikar, R.S.; Walimbe, A.M.; Jadhav, S.M.; Sudeep, A.B.; Mishra, A.C. Genetic divergence of Chikungunya viruses in India (1963–2006) with special reference to the 2005–2006 explosive epidemic. J. Gen. Virol., 2007, 88(7), 1967-1976.
[http://dx.doi.org/10.1099/vir.0.82714-0] [PMID: 17554030]
[21]
Ivanova, L.; Rausalu, K.; Žusinaite, E.; Tammiku-Taul, J.; Merits, A.; Karelson, M. 1,3-Thiazolbenzamide derivatives as Chikungunya Virus nsP2 protease inhibitors. ACS Omega, 2021, 6(8), 5786-5794.
[http://dx.doi.org/10.1021/acsomega.0c06191] [PMID: 33681617]
[22]
Álvarez, D.M.; Castillo, E.; Duarte, L.F.; Arriagada, J.; Corrales, N.; Farías, M.A.; Henríquez, A.; Agurto-Muñoz, C.; González, P.A. Current antivirals and novel botanical molecules interfering with Herpes simplex virus infection. Front. Microbiol., 2020, 11, 139.
[http://dx.doi.org/10.3389/fmicb.2020.00139] [PMID: 32117158]
[23]
Lolis, M.S.; González, L.; Cohen, P.J.; Schwartz, R.A. Drugresistant Herpes simplex virus in HIV infected patients Acta Dermatovenerol. Croat., 2008, 16(4), 204-208.
[PMID: 19111144]
[24]
Gudmundsson, K.S.; Johns, B.A.; Allen, S.H. Pyrazolopyridines with potent activity against herpesviruses: Effects of C5 substituents on antiviral activity. Bioorg. Med. Chem. Lett., 2008, 18(3), 1157-1161.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.120] [PMID: 18086523]
[25]
Sabbagh, E.; Baraka, M.M.; Ibrahim, S.M.; Pannecouque, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Rashad, A. Synthesis and antiviral activity of new pyrazole and thiazole derivatives Eur. J. Med. Chem., 2009, 44, 3746-3753.
[26]
Petrov, N.; Stoyanova, M.; Galabov, A. Inhibition of Coxsackievirus B3 cardiotropic strain Woodruff replication by silencing essential viral genes. Biotechnol. Biotechnol. Equip., 2019, 33(1), 1582-1589.
[http://dx.doi.org/10.1080/13102818.2019.1680318]
[27]
Real-Hohn, A.; Blaas, D. Rhinovirus inhibitors: Including a new target, the viral RNA. Viruses, 2021, 13(9), 1784.
[http://dx.doi.org/10.3390/v13091784] [PMID: 34578365]
[28]
Kaufmann, S.H.E.; Dorhoi, A.; Hotchkiss, R.S.; Bartenschlager, R. Host-directed therapies for bacterial and viral infections. Nat. Rev. Drug Discov., 2018, 17(1), 35-56.
[http://dx.doi.org/10.1038/nrd.2017.162] [PMID: 28935918]
[29]
Zumla, A.; Rao, M.; Wallis, R.S.; Kaufmann, S.H.E.; Rustomjee, R.; Mwaba, P.; Vilaplana, C.; Yeboah-Manu, D.; Chakaya, J.; Ippolito, G.; Azhar, E.; Hoelscher, M.; Maeurer, M. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect. Dis., 2016, 16(4), e47-e63.
[http://dx.doi.org/10.1016/S1473-3099(16)00078-5] [PMID: 27036359]
[30]
van de Wakker, S.I.; Fischer, M.J.E.; Oosting, R.S. New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections. Eur. J. Pharmacol., 2017, 809, 178-190.
[http://dx.doi.org/10.1016/j.ejphar.2017.05.038] [PMID: 28533172]
[31]
Ashraf, U.; Tengo, L.; Le Corre, L.; Fournier, G.; Busca, P.; McCarthy, A.A.; Rameix-Welti, M.A.; Gravier-Pelletier, C.; Ruigrok, R.W.H.; Jacob, Y.; Vidalain, P.O.; Pietrancosta, N.; Crépin, T.; Naffakh, N. Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy. Proc. Natl. Acad. Sci., 2019, 116(22), 10968-10977.
[http://dx.doi.org/10.1073/pnas.1901214116] [PMID: 31076555]
[32]
Ezeonwumelu, I.J.; Garcia-Vidal, E.; Ballana, E. JAK-STAT Pathway: A novel target to tackle viral infections. Viruses, 2021, 13(12), 2379.
[http://dx.doi.org/10.3390/v13122379] [PMID: 34960648]
[33]
Seif, F.; Aazami, H.; Khoshmirsafa, M.; Kamali, M.; Mohsenzadegan, M.; Pornour, M.; Mansouri, D. JAK inhibition as a new treatment strategy for patients with COVID-19. Int. Arch. Allergy Immunol., 2020, 181(6), 467-475.
[http://dx.doi.org/10.1159/000508247] [PMID: 32392562]
[34]
Saminathan, P.; Kevadiya, B.D.; Marker, D.F.; Gendelman, H.E.; Gorantla, S.; Gelbard, H.A. Broad spectrum mixed lineage kinase type 3 inhibition and HIV-1 persistence in macrophages. J. Neuroimmune Pharmacol., 2019, 14(1), 44-51.
[http://dx.doi.org/10.1007/s11481-018-09829-8] [PMID: 30617749]
[35]
Ahmadi Rastegar, D.; Dzamko, N. Leucine rich repeat kinase 2 and innate immunity. Front. Neurosci., 2020, 14, 193.
[http://dx.doi.org/10.3389/fnins.2020.00193] [PMID: 32210756]
[36]
Porichis, F.; Kaufmann, D.E. Role of PD-1 in HIV pathogenesis and as target for therapy. Curr. HIV/AIDS Rep., 2012, 9(1), 81-90.
[http://dx.doi.org/10.1007/s11904-011-0106-4] [PMID: 22198819]
[37]
Schönrich, G.; Raftery, M.J. The PD-1/PD-L1 axis and virus infections: A delicate balance. Front. Cell. Infect. Microbiol., 2019, 9, 207.
[http://dx.doi.org/10.3389/fcimb.2019.00207] [PMID: 31263684]
[38]
Cragg, G.M.; Newman, D.J. Natural products: A continuing source of novel drug leads. Biochim. Biophys. Acta, Gen. Subj., 2013, 1830(6), 3670-3695.
[http://dx.doi.org/10.1016/j.bbagen.2013.02.008]
[39]
Farghaly, T.A.; Alsaedi, A.M.R.; Alenazi, N.A.; Harras, M.F. Anti-viral activity of thiazole derivatives: an updated patent review. Expert Opin. Ther. Pat., 2022, 32(7), 791-815.
[http://dx.doi.org/10.1080/13543776.2022.2067477] [PMID: 35427454]
[40]
Lagoja, I.M. Pyrimidine as constituent of natural biologically active compounds. Chem. Biodivers., 2005, 2(1), 1-50.
[http://dx.doi.org/10.1002/cbdv.200490173] [PMID: 17191918]
[41]
Choudhury, A.; Chen, H.; Nilsen, C.N.; Sorgi, K.L. A chemoselective aniline–chloropyrimidine coupling in a competing electrophilic environment. Tetrahedron Lett., 2008, 49(1), 102-105.
[http://dx.doi.org/10.1016/j.tetlet.2007.11.009]
[42]
Brown, D.J. Pyrimidines and their benzo derivatives Compre. Heterocyclic Chem., 1984, 3, 57-155.
[43]
Aziz, M.A.; Serya, R.A.T.; Lasheen, D.S.; Abouzid, K.A.M. Furo[2,3-d]pyrimidine based derivatives as kinase inhibitors and anticancer agents. Fut. J. Pharm. Sci., 2016, 2(1), 1-8.
[http://dx.doi.org/10.1016/j.fjps.2015.12.001]
[44]
Padmaja, A.; Payani, T.; Reddy, G.D.; Padmavathi, V. Synthesis, antimicrobial and antioxidant activities of substituted pyrazoles, isoxazoles, pyrimidine and thioxopyrimidine derivatives. Eur. J. Med. Chem., 2009, 44(11), 4557-4566.
[http://dx.doi.org/10.1016/j.ejmech.2009.06.024] [PMID: 19631423]
[45]
Goodacre, S.C.; Street, L.J.; Hallett, D.J.; Crawforth, J.M.; Kelly, S.; Owens, A.P.; Blackaby, W.P.; Lewis, R.T.; Stanley, J.; Smith, A.J.; Ferris, P.; Sohal, B.; Cook, S.M.; Pike, A.; Brown, N.; Wafford, K.A.; Marshall, G.; Castro, J.L.; Atack, J.R. Imidazo[1,2-a]pyrimidines as functionally selective and orally bioavailable GABA(A)α2/α3 binding site agonists for the treatment of anxiety disorders. J. Med. Chem., 2006, 49(1), 35-38.
[http://dx.doi.org/10.1021/jm051065l] [PMID: 16392789]
[46]
Dansena, H.; Dhongade, H.; Chandrakar, K. Pharmacological potentials of pyrimidine derivative: a review Asian J. Pharm. Clin. Res., 2015, 8(4), 171-177.
[47]
Mohana Roopan, S.; Sompalle, R. Synthetic chemistry of pyrimidines and fused pyrimidines: A review. Synth. Commun., 2016, 46(8), 645-672.
[http://dx.doi.org/10.1080/00397911.2016.1165254]
[48]
Gordon, W.; John, A. A critical review of the 2005 literature preceded by two chapters on current heterocyclic topics Prog. Heterocyclic Chem., 2007, 18, 126-149.
[49]
Wang, S.; Yuan, X.H.; Wang, S.Q.; Zhao, W.; Chen, X.B.; Yu, B. FDA-approved pyrimidine-fused bicyclic heterocycles for cancer therapy: Synthesis and clinical application. Eur. J. Med. Chem., 2021, 214, 113218.
[http://dx.doi.org/10.1016/j.ejmech.2021.113218] [PMID: 33540357]
[50]
Khan, S.; Kale, M.; Siddiqui, F.; Nema, N. Novel pyrimidine-benzimidazole hybrids with antibacterial and antifungal properties and potential inhibition of SARS-CoV-2 main protease and spike glycoprotein. Digi. Chinese Med., 2021, 4(2), 102-119.
[http://dx.doi.org/10.1016/j.dcmed.2021.06.004]
[51]
Elgemeie, G.H.; Mohamed, R.A. Microwave chemistry: Synthesis of purine and pyrimidine nucleosides using microwave radiation. J. Carbohydr. Chem., 2019, 38(1), 20-66.
[http://dx.doi.org/10.1080/07328303.2018.1543430]
[52]
Winn, M.; Goss, R.J.M.; Kimura, K.; Bugg, T.D.H. Antimicrobial nucleoside antibiotics targeting cell wall assembly: Recent advances in structure–function studies and nucleoside biosynthesis. Nat. Prod. Rep., 2010, 27(2), 279-304.
[http://dx.doi.org/10.1039/B816215H] [PMID: 20111805]
[53]
Boutureira, O.; Matheu, M.I.; Díaz, Y.; Castillón, S. Advances in the enantioselective synthesis of carbocyclic nucleosides. Chem. Soc. Rev., 2013, 42(12), 5056-5072.
[http://dx.doi.org/10.1039/c3cs00003f] [PMID: 23471263]
[54]
Dziuba, D.; Pohl, R.; Hocek, M. Bodipy-labeled nucleoside triphosphates for polymerase synthesis of fluorescent DNA. Bioconjug. Chem., 2014, 25(11), 1984-1995.
[http://dx.doi.org/10.1021/bc5003554] [PMID: 25290695]
[55]
De Clercq, E.; Li, G. Approved antiviral drugs over the past 50 years. Clin. Microbiol. Rev., 2016, 29(3), 695-747.
[http://dx.doi.org/10.1128/CMR.00102-15] [PMID: 27281742]
[56]
Shelton, J.; Lu, X.; Hollenbaugh, J.A.; Cho, J.H.; Amblard, F.; Schinazi, R.F. Metabolism, biochemical actions, and chemical synthesis of anticancer nucleosides, KL. Chem. Rev., 2016, 116(23), 14379-14455.
[http://dx.doi.org/10.1021/acs.chemrev.6b00209] [PMID: 27960273]
[57]
Sari, O.; Roy, V.; Balzarini, J.; Snoeck, R.; Andrei, G.; Agrofoglio, L.A. Synthesis and antiviral evaluation of C5-substituted-(1,3-diyne)-2′-deoxyuridines. Eur. J. Med. Chem., 2012, 53, 220-228.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.001] [PMID: 22578783]
[58]
Clercq, E.D. Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster. Biochem. Pharmacol., 2004, 68(12), 2301-2315.
[http://dx.doi.org/10.1016/j.bcp.2004.07.039] [PMID: 15548377]
[59]
Cristofoli, W.A.; Wiebe, L.I.; De Clercq, E.; Andrei, G.; Snoeck, R.; Balzarini, J.; Knaus, E.E. 5-alkynyl analogs of arabinouridine and 2′-deoxyuridine: cytostatic activity against herpes simplex virus and varicella-zoster thymidine kinase gene-transfected cells. J. Med. Chem., 2007, 50(12), 2851-2857.
[http://dx.doi.org/10.1021/jm0701472] [PMID: 17518459]
[60]
Skorobogatyi, M.V. 5-Arylethynyl-2′-deoxyuridines, compounds active against HSV-1 Organic. Biomolecular. Chem., 2006, 4(6), 1091-1096.
[61]
Niu, H.Y.; Du, C.; Xie, M.S.; Wang, Y.; Zhang, Q.; Qu, G.R.; Guo, H.M. Diversity-oriented synthesis of acyclic nucleosides via ring-opening of vinyl cyclopropanes with purines. Chem. Commun., 2015, 51(16), 3328-3331.
[http://dx.doi.org/10.1039/C4CC09844G] [PMID: 25572827]
[62]
Krečmerová, M.; Dračínský, M.; Snoeck, R.; Balzarini, J.; Pomeisl, K.; Andrei, G. New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity. Bioorg. Med. Chem., 2017, 25(17), 4637-4648.
[http://dx.doi.org/10.1016/j.bmc.2017.06.046]
[63]
Bano, T.; Kumar, N.; Dudhe, R. Free radical scavenging properties of pyrimidine derivatives. Org. Med. Chem. Lett., 2012, 2(1), 34.
[http://dx.doi.org/10.1186/2191-2858-2-34] [PMID: 23151464]
[64]
Xu, A.; Zhou, N.; Zhang, X. Preparation and antiviral activity of pyrazolopyridinyl pyrimidines Faming Zhuanli Shenqing. Patent: CN 112724130 A, 2021.
[65]
Naffakh, N.; Crepin, T.; Vidalain, P.-O.; Pietrancosta, N.; Le Corre, L.; Busca, P.; Ashraf, U.; Corio, A.; Gravier-Pelletier, C. Antiviral and anti-cancer activity of pyrido[2,3-d]pyrimidine and oxadiazole compounds. Patent: EP 3722295 A1, 2020.
[66]
Naffakh, N.; Crepin, T.; Vidalain, P-O.; Pietrancosta, N.; Le Corre, L.; Busca, P.; Ashraf, U.; Corio, A.; Gravier-Pelletier, C. Anti-viral and anti-cancer activity of pyrido[2,3-d]pyrimidine and oxadiazole compounds. Patent:WO 2020208236 A1, 2020.
[67]
Kiselev, O. I.; Chupakhin, O. N.; Charushin, V. N.; Rusinov, V. L.; Deeva, E. G.; Ulomskii, E. N. Injection or infusion solution of Larginine salt of 5-methyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7- one monohydrate for therapy of influenza and other viral infections. Patent: RU 2586283 C1, 2016.
[68]
Chupakhin, O.N.; Rusinov, V.L.; Ulomskii, E.N.; Charushin, V.N.; Petrov, A.Yu.; Kiselev, O.I. Sodium salt 5-methyl-6-nitro- 1,2,4-triazole[1,5-a]pyrimidine-7-one dehydrate Patent:RU 2330036 C1, 2008.
[69]
Hu, Y.; Lou, L.; Cheng, G.; Xu, Y.; Xie, F.; Tang, W.; Li, J. Method for preparation of new type of small molecule pyrimidine derivatives with antitumor and antivirus activities. Patent:WO 2007104254 A1, 2007.
[70]
Li, A.; Jadaf, P. K.; Yao, Y.; Chen, Y.; Cao, G. Preparation of pyrimidinamine derivatives as Jak kinase inhibitor and used for preventing and/or treating diseases or disorders related to Jak kinase activity or expression, Faming Zhuanli Shenqing. Patent: CN 113372351 A, 2021.
[71]
Yao, Y.; Li, A.; Jadaf, P. K.; Cao, G. Preparation of (pyrimidinyl) thiadiazabicyclo[3.2.1]octane derivatives as JAK kinase inhibitor and used for preventing and/or treating diseases or disorders related to JAK kinase activity or expression. Patent: CN 113372364 A, 2021.
[72]
Kim, P. H.; Kim, S. H. Novel pyrimidine derivative and use thereof. WO 2021125803 A1 20210624, 2021.
[73]
Liu, Q.; Khosla, C.; Gupta, A. Enhancing the antiviral efficacy of RNA virus inhibition by combination with modulators of pyrimidine metabolism. Patent:WO 2021011572 A1, 2021.
[74]
Moesslacher, J.; Battisti, V.; Langer, T.; Urban, E.; Puerstinger, G.; Abdelnabi, R.; Delang, L.; Jochmans, D.; Leyssen, P.; Marchand, A. Preparation of substituted pyrimidinylpiperazines as antiviral compounds. Patent: WO 2020221894 A1, 2020.
[75]
Li, Y.; Li, Z.; Cen, S.; Peng, Z.; Li, J.; Wang, Y.; Quan, Y.; Zhou, R. Aroyl piperazine compounds with inhibitory activity to hepatitis C virus as well as Zika virus replication, preparation method and application thereof in antivirus. Patent: CN 110590708 A, 2019.
[76]
Kim, Jong U.; Lee, Sang Uk; Lee, Geun Hyeong; Han, Jae Jin; Park, Sang Jin; Park, Eul Yong; Shin, Jung Cheol Lim, Jong Hwan 2-(Methylthio)pyrimidine derivatives, their preparation method, and antiviral composition containing them, Repub. Patent: KR 2008061613 A, 2008.
[77]
Herdewijn, P.A.M.M.; De Jonghe, S.C.A.; Watkins, W.J.; Chong, L.S.; Zhang, J. Pyrido[3,2-d]pyrimidines as antiviral agents and their pharmaceutical compositions and use in the treatment of viral infections. Patent:WO 2008009076 A2, 2008.
[78]
Venkateshappa, C.; Duraiswamy, A.J.; Putta, R.K.V.P. Pyrimidine derivatives as inhibitors of PD1/PD-L1 activation and their preparation. Patent: IN 201741039535 A, 2019.
[79]
Pellacini, F.; Ungheri, D.; Schioppacassi, G.; Kraus, J-L.; Camplo, M.; Mourier, N.; Chermann, J-C. Preparation of pyrimidinone-1,3-oxathiolane nucleosides as antiviral agents. Patent:WO 9843972 A1, 1998.
[80]
Son, J. C.; Lee, I. Y.; Kim, H. S.; Kim, J. C.; Cho, E. H.; Chung, S. G.; Kim, J. Y.; Lee, S. H.; Kwon, H. S.; Lee, J. W. Preparation of 2,4-pyrimidinedione acyclic nucleosides as virucides for AIDS treatment. Patent: WO 9743266 A1, 1997.
[81]
Cho, E. H.; Chung, S. G.; Kim, J. Y.; Kwon, H. S.; Lee, S. H.; Lee, J. E.; Joo, J. H.; Kim, B. C.; Kang, D. W. Preparation of substituted pyrimidinedione homo-carbocyclic nucleosides as virucides. Patent: WO 9730979 A1, 1997.
[82]
D’cruz, O.; Uckun, F.M.; Venkatachalam, T. Preparation of AZT derivatives exhibiting spermicidal and anti-viral activity. US 20020025922 A1, 2002.
[83]
Wang, T.; Zhang, Z.; Meanwell, N.A.; Kadow, J.F.; Yin, Z.; Xue, Q.M.; Regueiro-Ren, A.; Matiskella, J.D.; Ueda, Y. Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives. Patent:US 20040110785 A1, 2004.
[84]
Son, J. C.; Lee, I. Y.; Bae, B. I.; Han, J. S.; Choi, J. K.; Chae, Y. B. Novel antiviral 2,4-pyrimidinedione derivatives and processes for the preparation thereof. Patent:WO 9518109 A1 19950706, 1995.
[85]
Gavegnano, C.; Schinazi, R.F. Antiviral pyrrolo[2,3-b]pyridine and pyrrolo[2,3-b]pyrimidine JAK inhibitors useful in treating or preventing retroviral and other viral infections. Patent:US 20190134039 A1, 2019.
[86]
Zhang, H.; Pan, T.; Luo, H.; Zhang, X.; Bai, C. Application of 1- (2-chlorophenyl)-4-{thieno [3,2-d]pyrimidin-4-yl} piperazine compound in preparing anti-HIV-1 drugs. Patent: CN 103893183 A, 2014.
[87]
Fan, X.; Zhang, X.; Li, X.; Wang, Y.; Xu, H.; Guo, S.; He, Y. 5- Substituted pyrimidine nucleoside-thiazolinone hybrid compound with anti-HIV activity and preparation method. Patent: CN 103242400 A, 2013.
[88]
Wang, Q.; Wang, C.; Li, Y.; Tan, J.; Wang, M.; Yao, X.; Qiao, W.; Geng, Y.; Liu, Y.; Wang, Li. Preparation of pyrimidineamide derivatives with anti-HIV and anti-TMV activity. Patent:A 20130605, 2013.
[89]
Chaltin, P.; Debyser, Z.; De Maeyer, M.; Marchand, A.; Marchand, D.; Smets, W.; Voet, A.; Christ, Fr. Pyrimidine derivatives as novel viral replication inhibitors and their preparation and use in the treatment of HIV infection. Patent: WO 2011015641 A1, 2011.
[90]
Wang, T.; Zhang, Z.; Meanwell, Ni. Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives. Patent: US 20030207910 A1, 2003.
[91]
Pedersen, E.B.; Jorgensen, P. Preparation of anti-retroviral 5,6- disubstituted acyclo-pyrimidine nucleoside derivatives Patent: WO 2003057677 A1, 2003.
[92]
Lori, F.; De Forni, D.; Stevens, M.R. Anti-proliferative substituted pyrazolo[3,4-d]pyrimidines derivatives (SPP) to inhibit immune activation, virus replication and tumor growth Patent: WO 2011014239 A1, 2011.
[93]
Cho, U. H.; Jung, S. G.; Myung, H. N.; Kwon, H. S.; Lee, S. H.; Lee, J. U.; Ju, J. Antiviral pyrimidinedione derivatives. Patent: KR 2007103536 A, 2007.
[94]
Zemlicka, J.; Qiu, Y.-l.; Drach, J. C.; Ptak, R. G. Preparation of 2- hydroxymethylcyclopropylidenemethylpurines and -pyrimidines as antiviral agents. Patent: S 6352991 B1, 2002.
[95]
Tets, V. V.; Tets, G. V.; Krasnov, K. A. Drug preparation with antiviral activity (versions). Patent: WO 2016159836 A1, 2016.
[96]
Chu, C. K.; Otto, M. J.; Shi, J.; Schinazi, R.F.; Choi, Y.; Gumina, G. Preparation, antiviral activity, and cytotoxicity of β-2'- and 3'- halo-nucleosides. Patent: WO 2003000200 A2, 2003.
[97]
Kim, J.W.; Chung, K.H.; Ahn, S.K.; Son, H.J.; Jeong, B.S. Preparation of nucleosides as anti-hepatitis-B virucides Patent:WO 9716456 A1, 1997.
[98]
Guo, X.; Tao, Y.; Li, Y.; Dong, L.; Liu, L.; Wang, Q.; Yu, X. 4-amino acid substituted pyrimidine nucleoside compound and application thereof in preparing antiviral myocarditis drugs and anticoxsackie virus drugs. Patent: CN 109265504 A, 2019.
[99]
Lancois, D. F. A.; Guillemont, J. E. G.; Raboisson, P. J.-M. B.; Roymans, D. A. E.; Rogovoy, B.; Bichko, V.; Lardeau, D. Y. R.; Michaut, A. B. Preparation of pyrazolo- and triazolo-pyrimidine compounds as RSV antiviral agents. Patent: WO 2016174079 A1, 2016.
[100]
Tahri, A.; Vendeville, S.M.H.; Jonckers, T.H.M.; Raboisson, P.J.-M.B.; Demin, S.D.; Hu, L. Preparation of piperidine substituted tricyclic pyrazolo[1,5-a]pyrimidine derivatives as respiratory syncytial virus inhibitors Patent: WO 2016091791 A1, 2016.
[101]
Tahri, A.; Vendeville, S. M. H.; Jonckers, T. H. M.; Raboisson, P. J.-M. B.; Demin, S. D.; Hu, L.; Cooymans, L. P. Preparation of piperidine substituted pyrazolo[1,5-a]pyrimidine derivatives as respiratory syncytial virus inhibitors. Patent: WO 2016091774 A1, 2016.
[102]
Wutzler, P.; Schmidtke, M.; Makarov, V. Process for production of 4-amino-3-arylamino-6-arylpyrazolo[3,4-d]pyrimidines. Patent: DE 102011116373 A1, 2013.
[103]
Yoshimura, Y.; Sato, H.; Matsuda, A.; Ashida, N.; Machida, H. Preparation of 2'-deoxy-2'-methylidene-4'-thiopyrimidine nucleosides as antiviral agents. Patent: JP 09087295 A, 1997.
[104]
Townsend, L. B.; Drach, J. C.; Renau, T. E. Pyrrolo[2,3-d]pyrimidine derivatives as antivirals. Patent: WO 9523151 A1, 1995.
[105]
Ashkinazi, R. I.; Ganina, M. B.; Studentsov, E. P. Bioactive substance containing derivatives of 2-amino-6-(aryloxy)pyrimidines and intermediate products of their synthesis. Patent: WO 2001019801 A1, 2001.
[106]
Herdewijn, P.; Wang, J.; De Clercq, E. Preparation of carbocyclic nucleosides as antiviral agents. Patent: WO 2001018003 A1, 2001.
[107]
Tets, V.V.; Tets, G.V.; Krutikov, V.I. Preparation of 2,4-dioxo-5-(2-hydroxy-3,5-dichlorobenzylidene)imino-1,3-pyrimidine sodium, potassium and ammonium salts having antimicrobial activity. Patent: RU 2260590 C1, 2005.
[108]
Hertel, L.W.; Kroin, J.S. 2'-deoxy-2',2'-difluoro-(4-substituted pyrimidine) nucleosides having antiviral and anti-cancer activity and intermediates. Patent: EP 576230 A1, 1993.
[109]
Townsend, L. B.; Drach, J. G.; Shipman, C., Jr; Pudlo, J. S. Preparation of acyclic pyrrolo(2,3-d)pyrimidine nucleoside analogs as antiviral agents. Patent: US 4968686 A, 1990.
[110]
Antiviral and antitumor-enhancing activities of pyrimidin-2-ones. Patent: US 940273 A0, 1987.
[111]
Bardos, T. J.; Cheng, Y. C.; Schroeder, A. C. Inhibition of the replication of DNA viruses with 5-substituted 2-pyrimidinone nucleosides. Patent: US 4468384 A, 1984.
[112]
Shealy, Y. Carbocyclic analogs of uracil nucleosides as antiviral agents. Patent: US 4396623 A, 1983.
[113]
Townsend, L.B.; Drach, J.C. Preparation of pyrrolo[2,3-d]pyrimidines as antiviral agents Patent: US 6342501 B1, 2002.
[114]
Balzarini, J.; Camarasa, M. J.; Velazquez, S. Improvements in or relating to compositions for the treatment or prophylaxis of viral infections, especially varicella zoster virus, by using nucleoside analogs esterified at 3 and/or 5 positions by neutral non-polar amino acid, or oligopeptide. Patent: WO 2009030410 A1, 2009.
[115]
Asraf, M.A.; Hossen, M.F.; Bitu, N.A.; Uddin, M.E.; Islam, M.R.; Zamir, R.; Zahan, M.K. Antiviral Compounds: A Road to Quest for Novel Antiviral Drugs Ann Med Chem, 2020, 1(1), 1004.
[116]
Kushwaha, N.; Sharma, C.S. The Chemistry of Triazine Isomers: Structures, Reactions, Synthesis and Applications. Mini Rev. Med. Chem., 2021, 20(20), 2104-2122.
[http://dx.doi.org/10.2174/1389557520666200729160720] [PMID: 32727324]
[117]
Andersen, P.I.; Ianevski, A.; Lysvand, H.; Vitkauskiene, A.; Oksenych, V.; Bjørås, M.; Telling, K.; Lutsar, I.; Dumpis, U.; Irie, Y.; Tenson, T.; Kantele, A.; Kainov, D.E. Discovery and development of safe-in-man broad-spectrum antiviral agents. Int. J. Infect. Dis., 2020, 93, 268-276.
[http://dx.doi.org/10.1016/j.ijid.2020.02.018] [PMID: 32081774]
[118]
Ghany, M.G.; Doo, E.C. Antiviral resistance and hepatitis B therapy. Hepatology, 2009, 49(S5), S174-S184.
[http://dx.doi.org/10.1002/hep.22900] [PMID: 19399794]
[119]
Zoulim, F. Hepatitis B virus resistance to antiviral drugs: where are we going? Liver Int., 2011, 31(1(S1)), 111-116.
[http://dx.doi.org/10.1111/j.1478-3231.2010.02399.x] [PMID: 21205147]
[120]
Wiehe, A.; O’Brien, J.M.; Senge, M.O. Trends and targets in antiviral phototherapy. Photochem. Photobiol. Sci., 2019, 18(11), 2565-2612.
[http://dx.doi.org/10.1039/c9pp00211a] [PMID: 31397467]
[121]
a) Ewers, E.C.; Shah, P.A.; Carmichael, M.G.; Ferguson, T.M. In Concurrent systemic chemo immunotherapy and sofosbuvir-based antiviral treatment in a hepatitis C virus-infected patient with diffuse large B-cell lymphoma. Open Forum Infect. Dis., 2016, 3(4), p. ofw223..
[http://dx.doi.org/10.1093/ofid/ofw223] [PMID: 28018926];
b) Fried, M.W. Side effects of therapy of hepatitis C and their management. Hepatology, 2002, 36(5)(Suppl. 1), S237-S244.
[PMID: 12407599]
[122]
Hanson, K.E.; Swaminathan, S. Cytomegalovirus antiviral drug resistance: future prospects for prevention, detection and management. Future Microbiol., 2015, 10(10), 1545-1548.
[http://dx.doi.org/10.2217/fmb.15.82] [PMID: 26437628]
[123]
Brennan, T.; Shrank, W. New expensive treatments for hepatitis C infection. JAMA, 2014, 312(6), 593-594.
[http://dx.doi.org/10.1001/jama.2014.8897] [PMID: 25038617]
[124]
Wu, D.; Wu, T.; Liu, Q.; Yang, Z. The SARS-CoV-2 outbreak: What we know. Int. J. Infect. Dis., 2020, 94, 44-48.
[http://dx.doi.org/10.1016/j.ijid.2020.03.004] [PMID: 32171952]
[125]
Li, X.; Wang, W.; Zhao, X.; Zai, J.; Zhao, Q.; Li, Y.; Chaillon, A. Transmission dynamics and evolutionary history of 2019-nCoV. J. Med. Virol., 2020, 92(5), 501-511.
[http://dx.doi.org/10.1002/jmv.25701] [PMID: 32027035]
[126]
Koszytkowska-Stawinska, M. Process for the preparation of new phosphono-substituted azanucleosides. Patent: PL 215487 B1, 2013.
[127]
Cornaglia, F. P.; Stradi, R. Preparation of pyrimidine derivatives with pharmacological activities. Patent: IT 91MI0978 A1, 1992.
[128]
Zhang, S.; Xiong, G. Antiviral composition of (R)-9-[2- (phosphorylmethoxy)propyl]adenine and (2R,cis)-4-amino-1-(2- hydroxymethyl-1,3-oxathiolan-5-yl)-pyrimidin-2-one. Patent: CN 101584701 A, 2009.
[129]
Balzarini, J.; Camarasa, M.J.; Velazquez, S. Improvements in or relating to compositions for the treatment or prophylaxis of viral infections, especially varicella zoster virus, by using nucleoside analogs esterified at 3 and/or 5 positions by neutral non-polar amino acid, or oligopeptide. Patent: GB 2452556 A, 2009.
[130]
Cho, D. G.; Cho, U. Y.; Choi, J. R.; Hwang, J. T.; Jang, H. S.; Kim, E. G.; Kim, J. M.; Lee, J. H.; Lim, J. H.; Noh, G. Y. Preparation of antiviral 2,4-pyrimidinedione derivatives. Patent: KR 2002074683 A, 2002.
[131]
Sonn, J. C.; Lee, I. Y.; Bae, B. I.; Han, J. S.; Choe, J. K.; Chae, Y. B. A novel process for the preparation of antiviral 2,4- pyrimidinedione derivatives. Patent: KR 151815 B1, 1998.
[132]
Loebering, H. G.; Miestereck, H. Pyrimidine nucleosides esterified in position 5' having antiviral activity and medicinal compositions containing them. Patent: EP 56265 A2, 1982.
[133]
Keppeler, K.; Kiefer, G. Substituted pyrimidine nucleosides with an antiviral activity and drug forms prepared with them. Patent: DE 3045375 A1, 1982.
[134]
Kiefer, G.; Keppeler, K. Substituted pyrimidine nucleosides with antiviral and cytostatic activity. Patent: DE 3045342 A1, 1982.
[135]
Grinev, A.N.; Kharizomenova, I.A.; Panisheva, E.K.; Tolstikova, E.V.; Bogdanova, N.S.; Nikolaeva, I.S.; Peters, V.V.; Pershin, G.N. Derivatives of 3-(p-benzoquinonylimino)-4-oxo-3,4- dihydrothieno[2,3-d]pyrimidine with antivirus activity. Patent: SU 677345 A1, 1980.
[136]
Slusarchyk, W. A.; Zahler, R. Preparation of an optically active [bis(hydroxymethyl)cyclobutyl]pyrimidine derivative as an antiviral agent. Patent: EP 484843 A1, 1992.
[137]
Kaplina, N. V.; Shvedov, V. I.; Fomina, A. N.; Nikolaeva, I. S.; Pushkina, T. V.; Filitis, L. N. Thieno-[2,3-d]pyrimidines having herpes virus inhibitory and antituberculosis activities. Patent: SU 1389235 A1, 1993.
[138]
Ichikawa, Y.; Ishikawa, F.; Matsuo, K.; Aoyama, K.; Nishiyama, Y.; Matsubara, K.; Nagahata, T.; Hoshino, H.; Seki, J. Preparation of 1-[3-(hydroxymethyl)cyclobutyl]pyrimidine derivatives as virucides. Patent: JP 02028161 A, 1990.
[139]
Marquez, V.E.; Driscoll, J.S. Preparation of cyclopentenylpyrimidine and -purine derivatives as antiviral and antitumor agents. Patent: US 307115 A0, 1989.
[140]
Takaku, H.; Yoshida, S.; Aoki, T.; Akiba, K. Preparation of acyclic nucleosides cyclic phosphoramidates having antiviral and anticancer activities. Patent: JP 63165373 A, 1988.
[141]
Holy, A.; Rosenberg, I.; De Clercq, E. Preparation and testing of N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases with antiviral activity Patent: EP 253412 A2, 1988.
[142]
Gatti, D. Pyrimidine derivatives endowed with antiviral activity. Patent: EP 124810 A1, 1984.
[143]
Jiang, C.; He, H.; Xu, L.; Lin, G. Preparation of anti-virus nucleoside analogs. Patent: CN 1563006 A, 2005.
[144]
Miyasaka, T.; Tanaka, H.; De Clercq, E.D.A.; Baba, M.; Walker, R.T.; Ubasawa, M. 6-substituted acyclic pyrimidine nucleoside derivatives and antiviral agents containing same as active ingredients. Patent: WO 8909213 A1, 1989.
[145]
Chiamenti, L.; Silva, F.P.; Schallemberger, K.; Demoliner, M.; Rigotto, C.; Fleck, J.D. Cytotoxicity and antiviral activity evaluation of Cymbopogon spp hydroethanolic extracts. Braz. J. Pharm. Sci., 2019, 55, e18063.
[http://dx.doi.org/10.1590/s2175-97902019000118063]

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