Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Synthetic Attempts Towards Eminent Anti-viral Candidates of SARS-CoV

Author(s): Subhradip Kundu and Debayan Sarkar*

Volume 22, Issue 2, 2022

Published on: 12 July, 2021

Page: [232 - 247] Pages: 16

DOI: 10.2174/1389557521666210712205655

Price: $65

Abstract

Abstract: Severe Acute Respiratory Syndrome (SARS) aka SARS-CoV spread over southern China for the first time in 2002-2003 and history repeated again since last year and took away lives of more than two million people so far. On March 11, 2020 COVID-19 outbreak was officially declared as pandemic by World Health Organization (WHO). The entire world united to fight back against this ultimate destruction. Around 90 vaccines are featured against SARS-CoV-2 and more than 300 active clinical trials are underway by several groups and individuals. So far, no drugs have been currently approved that can completely eliminate the deadly coronavirus. The promising SARS-CoV-2 antiviral drugs are favipiravir, remdesivir, lopinavir, ribavirin and avifavir. In this review, we have discussed the synthetic approaches elaborately made so far by different groups and chemical companies all around the world towards top three convincing anti-viral drugs against SARS-CoV-2, which are favipiravir, remdesivir and lopinavir.

Keywords: SARS-CoV, COVID-19, favipiravir, remdesivir, lopinavir, synthesis.

« Previous Next »
Graphical Abstract

[1]
Zumla, A.; Chan, J.F.W.; Azhar, E.I.; Hui, D.S.C.; Yuen, K.Y. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov., 2016, 15(5), 327-347.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[2]
Chan, J.F.W.; Lau, S.K.P.; Woo, P.C.Y. The emerging novel Middle East respiratory syndrome coronavirus: the “knowns” and “unknowns”. J. Formos. Med. Assoc., 2013, 112(7), 372-381.
[http://dx.doi.org/10.1016/j.jfma.2013.05.010] [PMID: 23883791]
[3]
Chan, J.F.W.; Li, K.S.M.; To, K.K.W.; Cheng, V.C.C.; Chen, H.; Yuen, K.Y. Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J. Infect., 2012, 65(6), 477-489.
[http://dx.doi.org/10.1016/j.jinf.2012.10.002] [PMID: 23072791]
[4]
Woo, P.C.Y.; Lau, S.K.P.; Huang, Y.; Yuen, K.Y. Coronavirus diversity, phylogeny and interspecies jumping. Exp. Biol. Med. (Maywood), 2009, 234(10), 1117-1127.
[http://dx.doi.org/10.3181/0903-MR-94] [PMID: 19546349]
[5]
Fan, Y.; Zhao, K.; Shi, Z.L.; Zhou, P. Bat Coronaviruses in China. Viruses, 2019, 11(3), 27-32.
[http://dx.doi.org/10.3390/v11030210] [PMID: 30832341]
[6]
Cheng, V.C.C.; Lau, S.K.P.; Woo, P.C.Y.; Yuen, K.Y. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin. Microbiol. Rev., 2007, 20(4), 660-694.
[http://dx.doi.org/10.1128/CMR.00023-07] [PMID: 17934078]
[7]
Lee, N.; Hui, D.; Wu, A.; Chan, P.; Cameron, P.; Joynt, G.M.; Ahuja, A.; Yung, M.Y.; Leung, C.B.; To, K.F.; Lui, S.F.; Szeto, C.C.; Chung, S.; Sung, J.J. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med., 2003, 348(20), 1986-1994.
[http://dx.doi.org/10.1056/NEJMoa030685] [PMID: 12682352]
[8]
Tsang, K.W.; Ho, P.L.; Ooi, G.C.; Yee, W.K.; Wang, T.; Chan-Yeung, M.; Lam, W.K.; Seto, W.H.; Yam, L.Y.; Cheung, T.M.; Wong, P.C.; Lam, B.; Ip, M.S.; Chan, J.; Yuen, K.Y.; Lai, K.N. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med., 2003, 348(20), 1977-1985.
[http://dx.doi.org/10.1056/NEJMoa030666] [PMID: 12671062]
[9]
Peiris, J.S.M.; Lai, S.T.; Poon, L.L.; Guan, Y.; Yam, L.Y.; Lim, W.; Nicholls, J.; Yee, W.K.; Yan, W.W.; Cheung, M.T.; Cheng, V.C.; Chan, K.H.; Tsang, D.N.; Yung, R.W.; Ng, T.K.; Yuen, K.Y. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet, 2003, 361(9366), 1319-1325.
[http://dx.doi.org/10.1016/S0140-6736(03)13077-2] [PMID: 12711465]
[10]
Drosten, C.; Günther, S.; Preiser, W.; van der Werf, S.; Brodt, H.R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R.A.; Berger, A.; Burguière, A.M.; Cinatl, J.; Eickmann, M.; Escriou, N.; Grywna, K.; Kramme, S.; Manuguerra, J.C.; Müller, S.; Rickerts, V.; Stürmer, M.; Vieth, S.; Klenk, H.D.; Osterhaus, A.D.; Schmitz, H.; Doerr, H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med., 2003, 348(20), 1967-1976.
[http://dx.doi.org/10.1056/NEJMoa030747] [PMID: 12690091]
[11]
Ksiazek, T.G.; Erdman, D.; Goldsmith, C.S.; Zaki, S.R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J.A.; Lim, W.; Rollin, P.E.; Dowell, S.F.; Ling, A.E.; Humphrey, C.D.; Shieh, W.J.; Guarner, J.; Paddock, C.D.; Rota, P.; Fields, B.; DeRisi, J.; Yang, J.Y.; Cox, N.; Hughes, J.M.; LeDuc, J.W.; Bellini, W.J.; Anderson, L.J. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med., 2003, 348(20), 1953-1966.
[http://dx.doi.org/10.1056/NEJMoa030781] [PMID: 12690092]
[12]
World Health Organization. Summary of Probable SARS Cases with Onset of Illness from November 1, 2002 to July 31, 2003., 2003.
[13]
Singh, A.K.; Singh, A.; Shaikh, A.; Singh, R.; Misra, A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab. Syndr., 2020, 14(3), 241-246.
[http://dx.doi.org/10.1016/j.dsx.2020.03.011] [PMID: 32247211]
[14]
Moscatelli, A. Chemistry under nanoconfinement. Nat. Nanotechnol., 2020, 15(4), 239.
[http://dx.doi.org/10.1038/s41565-020-0664-y] [PMID: 32303703]
[15]
World Health Organization Live Updates of WHO.Available from:, https://doi.org/https://covid19.who.int/?gclid=Cj0KCQjwoPL2BRDxARI-sAEMm9y8gieRZ108j8bDB_AtpwxG9y8pUFnFy9g_sTRiBN-pnE4CILVOcMJMaAtLfEALw_wcB
[16]
World Health Organization Director General’s Opening Remarks at the Media Briefing on COVID-19 on March 11, 2020. 2020.,
[17]
So, L.K.Y.; Lau, A.C.W.; Yam, L.Y.C.; Cheung, T.M.T.; Poon, E.; Yung, R.W.H.; Yuen, K.Y. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet, 2003, 361(9369), 1615-1617.
[http://dx.doi.org/10.1016/S0140-6736(03)13265-5] [PMID: 12747883]
[18]
Kilianski, A.; Baker, S.C. Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors. Antiviral Res., 2014, 101, 105-112.
[http://dx.doi.org/10.1016/j.antiviral.2013.11.004] [PMID: 24269477]
[19]
Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA, 2020, 323(18), 1824-1836.
[PMID: 32282022]
[20]
(a)Callaway, E. The race for vaccines. Nature, 2020, 580, 576-577.,
[http://dx.doi.org/10.1038/d41586-020-01221-y] [PMID: 32346146]
(b)Hadi, A. G. In COVID-19 time, how to protect myself and others? A review. Jurnal Biomedika dan Kesehatan, 2020, 3(3), 153-158.,
(c)Hadi, A.G. A review on covid-19: Origin, spread, symptoms, treatment, and prevention. Biointerface Research in Applied Chemistry, 2020, 10(6), 7234-7242.
[http://dx.doi.org/10.33263/BRIAC106.72347242]
[21]
Cai, Q.; Yang, M.; Liu, D.; Chen, J.; Shu, D.; Xia, J.; Liao, X.; Gu, Y.; Cai, Q.; Yang, Y.; Shen, C.; Li, X.; Peng, L.; Huang, D.; Zhang, J.; Zhang, S.; Wang, F.; Liu, J.; Chen, L.; Chen, S.; Wang, Z.; Zhang, Z.; Cao, R.; Zhong, W.; Liu, Y.; Liu, L. Experimental treatment with favipiravir for covid-19: An open-label control study. Engineering (Beijing), 2020, 6(10), 1192-1198.
[http://dx.doi.org/10.1016/j.eng.2020.03.007] [PMID: 32346491]
[22]
Booth, C.M.; Matukas, L.M.; Tomlinson, G.A.; Rachlis, A.R.; Rose, D.B.; Dwosh, H.A.; Walmsley, S.L.; Mazzulli, T.; Avendano, M.; Derkach, P.; Ephtimios, I.E.; Kitai, I.; Mederski, B.D.; Shadowitz, S.B.; Gold, W.L.; Hawryluck, L.A.; Rea, E.; Chenkin, J.S.; Cescon, D.W.; Poutanen, S.M.; Detsky, A.S. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA, 2003, 289(21), 2801-2809.
[http://dx.doi.org/10.1001/jama.289.21.JOC30885] [PMID: 12734147]
[23]
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N. Engl. J. Med., 2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[24]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[25]
Furuta, Y.; Egawa, H.; Takahashi, K.; Tsutsui, Y.; Uehara, S.; Muratami, M. Nitrogenous heterocyclic carboxamide derivatives or salts thereof and antiviral agents containing both. EU Patent WO 00/10569,, 2000.
[26]
Furuta, Y.; Takahashi, K.; Shiraki, K.; Sakamoto, K.; Smee, D.F.; Barnard, D.L.; Gowen, B.B.; Julander, J.G.; Morrey, J.D. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res., 2009, 82(3), 95-102.
[http://dx.doi.org/10.1016/j.antiviral.2009.02.198] [PMID: 19428599]
[27]
Liu, F.L.; Li, C.Q.; Xiang, H.Y.; Feng, S. A practical and step-economic route to favipiravir. Chem. Pap., 2017, 71(11), 2153-2158.
[http://dx.doi.org/10.1007/s11696-017-0208-6]
[28]
Guo, Q.; Xu, M.; Guo, S.; Zhu, F.; Xie, Y.; Shen, J. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. Pap., 2019, 73(5), 1043-1051.
[http://dx.doi.org/10.1007/s11696-018-0654-9]
[29]
Smither, S.J.; Eastaugh, L.S.; Steward, J.A.; Nelson, M.; Lenk, R.P.; Lever, M.S. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res., 2014, 104(1), 153-155.
[http://dx.doi.org/10.1016/j.antiviral.2014.01.012] [PMID: 24462697]
[30]
Oestereich, L.; Lüdtke, A.; Wurr, S.; Rieger, T.; Muñoz-Fontela, C.; Günther, S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res., 2014, 105(1), 17-21.
[http://dx.doi.org/10.1016/j.antiviral.2014.02.014] [PMID: 24583123]
[31]
Yamada, K.; Noguchi, K.; Komeno, T.; Furuta, Y.; Nishizono, A. Efficacy of favipiravir (t-705) in rabies postexposure prophylaxis. J. Infect. Dis., 2016, 213(8), 1253-1261.
[http://dx.doi.org/10.1093/infdis/jiv586] [PMID: 26655300]
[32]
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]
[33]
Jin, Z.; Tucker, K.; Lin, X.; Kao, C.C.; Shaw, K.; Tan, H.; Symons, J.; Behera, I.; Rajwanshi, V.K.; Dyatkina, N.; Wang, G.; Beigelman, L.; Deval, J. Biochemical evaluation of the inhibition properties of favipiravir and 2′-c-methyl-cytidine triphosphates against human and mouse norovirus rna polymerases. Antimicrob. Agents Chemother., 2015, 59(12), 7504-7516.
[http://dx.doi.org/10.1128/AAC.01391-15] [PMID: 26392512]
[34]
El-Nahas, A.M.; Hirao, K. A theoretical study on 2-hydroxypyrazine and 2,3-dihydroxypyrazine: Tautomerism, intramolecular hydrogen bond, solvent effects. J. Mol. Struct. THEOCHEM, 1999, 459, 229-237.
[http://dx.doi.org/10.1016/S0166-1280(98)00270-X]
[35]
Beldar, S.; Jordis, U. Synthetic studies towards the antiviral pyrazine derivative t-705. 13th Electronic conference on synthetic organic chemistry (ECSOC-13), 2009.
[36]
Hara, T. Method for producing dichloropyrazine derivative. US Patent 20110275817A1,, 2011.
[37]
Caldwell, J.J.; Veillard, N.; Collins, I. Design and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases. Tetrahedron, 2012, 68(47), 9713-9728.
[http://dx.doi.org/10.1016/j.tet.2012.09.039]
[38]
Shi, F.; Li, Z.; Kong, L.; Xie, Y.; Zhang, T.; Xu, W. Synthesis and crystal structure of 6-fluoro-3-hydroxypyrazine-2-carboxamide. Drug Discov. Ther., 2014, 8(3), 117-120.
[http://dx.doi.org/10.5582/ddt.2014.01028] [PMID: 25031043]
[39]
Wan, W. Synthesis of favipiravir. Int. J. Pharm. Res., 2015, 42(2), 220-224.
[40]
Tao, Z.; Lingjin, K.; Zongtao, L.I.; Hongyu, Y.; Wenfang, X.U. Synthesis of favipiravir. Chinese J. Pharm., 2013, 44(9), 841-843.
[41]
Wang, H.; Xingzhou, L.; Zhong, W. Synthesis of favipiravir. Chinese J. Pharm., 2014, 11, 1009-1012.
[42]
Warren, T.K.; Jordan, R.; Lo, M.K.; Ray, A.S.; Mackman, R.L.; Soloveva, V.; Siegel, D.; Perron, M.; Bannister, R.; Hui, H.C.; Larson, N.; Strickley, R.; Wells, J.; Stuthman, K.S.; Van Tongeren, S.A.; Garza, N.L.; Donnelly, G.; Shurtleff, A.C.; Retterer, C.J.; Gharaibeh, D.; Zamani, R.; Kenny, T.; Eaton, B.P.; Grimes, E.; Welch, L.S.; Gomba, L.; Wilhelmsen, C.L.; Nichols, D.K.; Nuss, J.E.; Nagle, E.R.; Kugelman, J.R.; Palacios, G.; Doerffler, E.; Neville, S.; Carra, E.; Clarke, M.O.; Zhang, L.; Lew, W.; Ross, B.; Wang, Q.; Chun, K.; Wolfe, L.; Babusis, D.; Park, Y.; Stray, K.M.; Trancheva, I.; Feng, J.Y.; Barauskas, O.; Xu, Y.; Wong, P.; Braun, M.R.; Flint, M.; McMullan, L.K.; Chen, S.S.; Fearns, R.; Swaminathan, S.; Mayers, D.L.; Spiropoulou, C.F.; Lee, W.A.; Nichol, S.T.; Cihlar, T.; Bavari, S. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 2016, 531(7594), 381-385.
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[43]
Cho, A.; Saunders, O.L.; Butler, T.; Zhang, L.; Xu, J.; Vela, J.E.; Feng, J.Y.; Ray, A.S.; Kim, C.U. Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides. Bioorg. Med. Chem. Lett., 2012, 22(8), 2705-2707.
[http://dx.doi.org/10.1016/j.bmcl.2012.02.105] [PMID: 22446091]
[44]
Murakami, E.; Niu, C.; Bao, H.; Micolochick Steuer, H.M.; Whitaker, T.; Nachman, T.; Sofia, M.A.; Wang, P.; Otto, M.J.; Furman, P.A. The mechanism of action of β-D-2′-deoxy-2′-fluoro-2′-C-methylcytidine involves a second metabolic pathway leading to β-D-2′-deoxy-2′-fluoro-2′-C-methyluridine 5′-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob. Agents Chemother., 2008, 52(2), 458-464.
[http://dx.doi.org/10.1128/AAC.01184-07] [PMID: 17999967]
[45]
Mackman, R.L. Methods and compounds for treating paramyxoviridae virus infections. US Patent WO2012/012776 A1,, 2011.
[46]
Siegel, D.; Hui, H.C.; Doerffler, E.; Clarke, M.O.; Chun, K.; Zhang, L.; Neville, S.; Carra, E.; Lew, W.; Ross, B.; Wang, Q.; Wolfe, L.; Jordan, R.; Soloveva, V.; Knox, J.; Perry, J.; Perron, M.; Stray, K.M.; Barauskas, O.; Feng, J.Y.; Xu, Y.; Lee, G.; Rheingold, A.L.; Ray, A.S.; Bannister, R.; Strickley, R.; Swaminathan, S.; Lee, W.A.; Bavari, S.; Cihlar, T.; Lo, M.K.; Warren, T.K.; Mackman, R.L. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine c-nucleoside (gs-5734) for the treatment of ebola and emerging viruses. J. Med. Chem., 2017, 60(5), 1648-1661.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01594] [PMID: 28124907]
[47]
Al-Tawfiq, J.A.; Al-Homoud, A.H.; Memish, Z.A. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med. Infect. Dis., 2020, 34101615
[http://dx.doi.org/10.1016/j.tmaid.2020.101615] [PMID: 32145386]
[48]
Harrison, C. Coronavirus puts drug repurposing on the fast track. Nat. Biotechnol., 2020, 38(4), 379-381.
[http://dx.doi.org/10.1038/d41587-020-00003-1] [PMID: 32205870]
[49]
Ramasamy, K.; Ugarkar, B.G.; McKernan, P.A.; Robins, R.K.; Revankar, G.R. Synthesis and antitumor activity of certain 3-β-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazines related to formycin prepared via ring closure of a 1,2,4-triazine precursor. J. Med. Chem., 1986, 29(11), 2231-2235.
[http://dx.doi.org/10.1021/jm00161a017] [PMID: 3783585]
[50]
Patil, S.A.; Otter, B.A.; Klein, R.S. 4-aza-7,9-dideazaadenosine, a new cytotoxic synthetic c-nucleoside analogue of adenosine. Tetrahedron Lett., 1994, 35(30), 5339-5342.
[http://dx.doi.org/10.1016/S0040-4039(00)73494-0]
[51]
Otter, B.A.; Klein, R.S. Conformational properties of purine-like c-nucleosides. Nucleosides Nucleotides, 1996, 15, 793-807.
[http://dx.doi.org/10.1080/07328319608002423]
[52]
Nishimura, N.; Kato, A.; Maeba, I. Synthesis of pyrrolo[2,1-f][1,2,4]triazine C-nucleosides. Isosteres of sangivamycin, tubercidin, and toyocamycin. Carbohydr. Res., 2001, 331(1), 77-82.
[http://dx.doi.org/10.1016/S0008-6215(01)00017-9] [PMID: 11284507]
[53]
Butler, T. 1’-substituted carba-nucleoside analogs for antiviral research. US Patent WO2009/132135 A1,, 2009.
[54]
Butler, T. . Process and intermediates for the preparation of 1’- substituted carba-nucleoside analogs. US Patent WO2011/035250 A1,, 2010.
[55]
Metobo, S.E.; Xu, J.; Saunders, O.L.; Butler, T.; Aktoudianakis, E.; Cho, A.; Kim, C.U. Practical synthesis of 1′-substituted tubercidin c-nucleoside analogs. Tetrahedron Lett., 2012, 53(5), 484-486.
[http://dx.doi.org/10.1016/j.tetlet.2011.11.055]
[56]
Clarke, M.O.H. Methods for treating arenaviridae and coronaviridae virus infections. US Patent 10,251,904 B2,, 2016.
[57]
Clarke, M.O.H. Methods for treating flaviviridae virus infections. US Patent WO 2017/184668 A1,, 2017.
[58]
Brak, K. Crystalline forms of (s)-2-ethylbutyl-2-((s)-(((2r,3s,4r,5r)- 5-(4-aminopyrolo[1,2,4]triazin-7-yl)-5-cyano-3,4- dihydroxytetrahydrofuran-2-yl) methoxy) (phenoxy) phosphoryl) amino) propanoate. US Patent WO 2018/204198 A1,, 2018.
[59]
Encinar, J.A.; Menendez, J.A. Potential drugs targeting early innate immune evasion of sars-coronavirus 2 via 2′-o-methylation of viral RNA. Viruses, 2020, 12(5), 525-550.
[http://dx.doi.org/10.3390/v12050525] [PMID: 32397643]
[60]
Beigel, J.H.; Tomashek, K.M.; Dodd, L.E. Remdesivir for the treatment of covid-19 - preliminary report. Reply. N. Engl. J. Med., 2020, 383(10), 994.
[PMID: 32649078]
[61]
Deeks, S.G.; Smith, M.; Holodniy, M.; Kahn, J.O. HIV-1 protease inhibitors. A review for clinicians. JAMA, 1997, 277(2), 145-153.
[http://dx.doi.org/10.1001/jama.1997.03540260059037] [PMID: 8990341]
[62]
Molla, A.; Vasavanonda, S.; Kumar, G.; Sham, H.L.; Johnson, M.; Grabowski, B.; Denissen, J.F.; Kohlbrenner, W.; Plattner, J.J.; Leonard, J.M.; Norbeck, D.W.; Kempf, D.J. Human serum attenuates the activity of protease inhibitors toward wild-type and mutant human immunodeficiency virus. Virology, 1998, 250(2), 255-262.
[http://dx.doi.org/10.1006/viro.1998.9383] [PMID: 9792836]
[63]
Kempf, D.J. ABT-538 inhibitor high bioavailability. Proc. Natl. Acad. Sci. USA, 1995, 92, 2484-2488.
[http://dx.doi.org/10.1073/pnas.92.7.2484] [PMID: 7708670]
[64]
Kempf, D.J.; Sham, H.L.; Marsh, K.C.; Flentge, C.A.; Betebenner, D.; Green, B.E.; McDonald, E.; Vasavanonda, S.; Saldivar, A.; Wideburg, N.E.; Kati, W.M.; Ruiz, L.; Zhao, C.; Fino, L.; Patterson, J.; Molla, A.; Plattner, J.J.; Norbeck, D.W. Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy. J. Med. Chem., 1998, 41(4), 602-617.
[http://dx.doi.org/10.1021/jm970636+] [PMID: 9484509]
[65]
Sham, H.L.; Kempf, D.J.; Molla, A.; Marsh, K.C.; Kumar, G.N.; Chen, C.M.; Kati, W.; Stewart, K.; Lal, R.; Hsu, A.; Betebenner, D.; Korneyeva, M.; Vasavanonda, S.; McDonald, E.; Saldivar, A.; Wideburg, N.; Chen, X.; Niu, P.; Park, C.; Jayanti, V.; Grabowski, B.; Granneman, G.R.; Sun, E.; Japour, A.J.; Leonard, J.M.; Plattner, J.J.; Norbeck, D.W. ABT-378, A highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob. Agents Chemother., 1998, 42(12), 3218-3224.
[http://dx.doi.org/10.1128/AAC.42.12.3218] [PMID: 9835517]
[66]
Chu, C.M.; Cheng, V.C.; Hung, I.F.; Wong, M.M.; Chan, K.H.; Chan, K.S.; Kao, R.Y.; Poon, L.L.; Wong, C.L.; Guan, Y.; Peiris, J.S.; Yuen, K.Y. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax, 2004, 59(3), 252-256.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[67]
Sham, H.L.; Betebenner, D.A.; Chen, X.; Saldivar, A.; Vasavanonda, S.; Kempf, D.J.; Plattner, J.J.; Norbeck, D.W. Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir). Bioorg. Med. Chem. Lett., 2002, 12(8), 1185-1187.
[http://dx.doi.org/10.1016/S0960-894X(02)00134-8] [PMID: 11934584]
[68]
Carrillo, A.; Stewart, K.D.; Sham, H.L.; Norbeck, D.W.; Kohlbrenner, W.E.; Leonard, J.M.; Kempf, D.J.; Molla, A. In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. J. Virol., 1998, 72(9), 7532-7541.
[http://dx.doi.org/10.1128/JVI.72.9.7532-7541.1998] [PMID: 9696850]
[69]
Stoner, E.J.; Stengel, P.J.; Cooper, A.J. Synthesis of abt-378, an hiv protease inhibitor candidate: Avoiding the use of carbodiimides in a difficult peptide coupling. Org. Process Res. Dev., 1999, 3(2), 145-148.
[http://dx.doi.org/10.1021/op980214p]
[70]
Stoner, E.J. Synthesis of hiv protease inhibitor abt-378 (lopinavir). Org. Process Res. Dev., 2000, 4(4), 264-269.
[http://dx.doi.org/10.1021/op990202j]
[71]
Sham, H.L.; Betebenner, D.A.; Herrin, T.; Kumar, G.; Saldivar, A.; Vasavanonda, S.; Molla, A.; Kempf, D.J.; Plattner, J.J.; Norbeck, D.W. Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir). Bioorg. Med. Chem. Lett., 2001, 11(11), 1351-1353.
[http://dx.doi.org/10.1016/S0960-894X(01)00243-8] [PMID: 11378352]
[72]
Raghava Reddy, A.V.; Garaga, S.; Takshinamoorthy, C.; Naidu, A. Synthesis and characterization of impurities in the production process of lopinavir. Sci. Pharm., 2014, 83(1), 49-63.
[http://dx.doi.org/10.3797/scipharm.1407-14] [PMID: 26839801]
[73]
Kellow, R.; Matziari, M. Synthesis of a new lopinavir phosphinic analog as hiv-1 inhibitor. J. Mater. Sci. Chem. Eng., 2019, 7, 36-41.
[http://dx.doi.org/10.4236/msce.2019.77005]

Rights & Permissions Print Cite
Article Metrics
52
10
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy