Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

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

Mini-Review Article

Drug Re-purposing Approach and Potential Therapeutic Strategies to Treat COVID-19

Author(s): Eeda Koti Reddy, Srisravanthi Battula, Shaik Anwar* and Ayyiliath M Sajith*

Volume 21, Issue 6, 2021

Published on: 13 November, 2020

Page: [704 - 723] Pages: 20

DOI: 10.2174/1389557520666201113105940

Price: $65

Abstract

The current pandemic of COVID-19 caused by SARS-Cov-2 has posed a severe threat to the whole world with its highly infectious, progressive nature with up to 10% mortality rates. The severity of the situation faced by the whole world and the lack of efficient therapeutics to treat this viral disease have led the WHO to depend on the drug-repurposing approach to tackle this major global health problem. This review aims at highlighting the various synthetic approaches employed for the synthesis of these FDA approved drugs that have been presently used for COVID-19 treatment. Additionally, a brief overview of several therapeutic strategies is also presented. This review will encourage the scientific community across the globe to come up with better and efficient synthetic protocols and also novel chemical entities along with this core with more potent activity.

Keywords: SARS-Cov-2, COVID-19, betacoronavirus, epidemiological, acute respiratory syndrome, FDA.

Graphical Abstract

[1]
Gorbalenya, A.E.; Baker, S.C. et al. Coronaviridae study group of the international committee on taxonomy of viruses. The species severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microb,., 2020, 5(4), 536-544. doi: 10.1038/s41564-020-0695-z. Epub 2020 Mar 2. PMID: 32123347; PMCID: PMC7095448.
[http://dx.doi.org/10.1038/s41564-020-0695-z] [PMID: 32123347]
[2]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[3]
Wu, F.; Zhao, S.; Yu, B.; Chen, Y.M.; Wang, W.; Song, Z.G.; Hu, Y.; Tao, Z.W.; Tian, J.H.; Pei, Y.Y.; Yuan, M.L.; Zhang, Y.L.; Dai, F.H.; Liu, Y.; Wang, Q.M.; Zheng, J.J.; Xu, L.; Holmes, E.C.; Zhang, Y.Z. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798), 265-269.
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[5]
(a)Li, W.; Shi, Z.; Yu, M.; Ren, W.; Smith, C.; Epstein, J.H.; Wang, H.; Crameri, G.; Hu, Z.; Zhang, H.; Zhang, J.; McEachern, J.; Field, H.; Daszak, P.; Eaton, B.T.; Zhang, S.; Wang, L.F. Bats are natural reservoirs of SARS-like coronaviruses. Science, 2005, 310(5748), 676-679.
[http://dx.doi.org/10.1126/science.1118391] [PMID: 16195424]
(b)Ge, X.Y.; Li, J.L.; Yang, X.L.; Chmura, A.A.; Zhu, G.; Epstein, J.H.; Mazet, J.K.; Hu, B.; Zhang, W.; Peng, C.; Zhang, Y.J.; Luo, C.M.; Tan, B.; Wang, N.; Zhu, Y.; Crameri, G.; Zhang, S.Y.; Wang, L.F.; Daszak, P.; Shi, Z.L. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature, 2013, 503(7477), 535-538.
[http://dx.doi.org/10.1038/nature12711] [PMID: 24172901]
(c)Yang, L.; Wu, Z.; Ren, X.; Yang, F.; He, G.; Zhang, J.; Dong, J.; Sun, L.; Zhu, Y.; Du, J.; Zhang, S.; Jin, Q. Novel SARS-like betacoronaviruses in bats, China, 2011. Emerg. Infect. Dis., 2013, 19(6), 989-991.
[http://dx.doi.org/10.3201/eid1906.121648] [PMID: 23739658]
(d)Menachery, V.D.; Yount, B.L., Jr; Debbink, K.; Agnihothram, S.; Gralinski, L.E.; Plante, J.A.; Graham, R.L.; Scobey, T.; Ge, X.Y.; Donaldson, E.F.; Randell, S.H.; Lanzavecchia, A.; Marasco, W.A.; Shi, Z.L.; Baric, R.S. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med., 2015, 21(12), 1508-1513.
[http://dx.doi.org/10.1038/nm.3985] [PMID: 26552008]
(e)Wang, N.; Li, S.Y.; Yang, X.L.; Huang, H.M.; Zhang, Y.J.; Guo, H.; Luo, C.M.; Miller, M.; Zhu, G.; Chmura, A.A.; Hagan, E.; Zhou, J.H.; Zhang, Y.Z.; Wang, L.F.; Daszak, P.; Shi, Z.L. Serological evidence of bat SARS- related coronavirus infection in humans, China. Virol. Sin., 2018, 33(1), 104-107.
[http://dx.doi.org/10.1007/s12250-018-0012-7] [PMID: 29500691]
[6]
Chafekar, A.; Fielding, B.C. MERS-CoV: Understanding the latest human Coronavirus threat. Viruses, 2018, 10(2), 93.
[http://dx.doi.org/10.3390/v10020093]
[7]
Shi, M.; Lin, X.D.; Tian, J.H.; Chen, L.J.; Chen, X.; Li, C.X.; Qin, X.C.; Li, J.; Cao, J.P.; Eden, J.S.; Buchmann, J.; Wang, W.; Xu, J.; Holmes, E.C.; Zhang, Y.Z. Redefining the invertebrate RNA virosphere. Nature, 2016, 540(7634), 539-543.
[http://dx.doi.org/10.1038/nature20167] [PMID: 27880757]
[8]
Guo, Y.R.; Cao, Q.D.; Hong, Z.S.; Tan, Y.Y.; Chen, S.D.; Jin, H.J.; Tan, K.S.; Wang, D.Y.; Yan, Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil. Med. Res., 2020, 7(1), 11.
[http://dx.doi.org/10.1186/s40779-020-00240-0] [PMID: 32169119]
[9]
Ghosh, A.K.; Brindisi, M.; Shahabi, D.; Chapman, M.E.; Mesecar, A.D. Drug Development and Medicinal Chemistry Efforts Toward SARS-Coronavirus and Covid-19 Therapeutics. ChemMedChem, 2020, 15(11), 907-932.
[http://dx.doi.org/10.1002/cmdc.202000223]]
[10]
(a)Ratia, K.; Saikatendu, K.S.; Santarsiero, B.D.; Barretto, N.; Baker, S.C.; Stevens, R.C.; Mesecar, A.D. Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme. Proc. Natl. Acad. Sci. USA, 2006, 103(15), 5717-5722.
[http://dx.doi.org/10.1073/pnas.0510851103] [PMID: 16581910]
(b)Zumla, A.; Chan, J.F.; Azhar, E.I.; Hui, D.S.; 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]
[11]
Costanzo, M.; De Giglio, M.A.R.; Roviello, G.N. SARS-CoV-2: Recent reports on antiviral therapies based on lopinavir/ritonavir, darunavir/umifenovir, hydroxychloroquine, remdesivir, favipiravir and other drugs for the treatment of the new coronavirus. Curr. Med. Chem., 2020, 27(27), 4536-4541.
[http://dx.doi.org/10.2174/0929867327666200416131117.]] [PMID: 32297571.]
[12]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[13]
Mousavizadeh, L; Ghasemi, S S. Genotype and phenotype of COVID- 19: Their roles in pathogenesis. J. Microbiol. Immunol. Infect.., 2020, S1684-S1182(20), 30082-30087. 10.1016/j.jmii.2020.03.022. Epub ahead of print. PMID: 32265180; PMCID: PMC7138183.
[14]
(a)Su, S.; Wong, G.; Shi, W.; Liu, J.; Lai, A.C.K.; Zhou, J.; Liu, W.; Bi, Y.; Gao, G.F. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol., 2016, 24(6), 490-502.,
[http://dx.doi.org/10.1016/j.tim.2016.03.003] [PMID: 27012512]
(b)Hung, I.F.; Lung, K.C.; Tso, E.Y.; Liu, R.; Chung, T.W.; Chu, M.Y.; Ng, Y.Y.; Lo, J.; Chan, J.; Tam, A.R.; Shum, H.P.; Chan, V.; Wu, A.K.; Sin, K.M.; Leung, W.S.; Law, W.L.; Lung, D.C.; Sin, S.; Yeung, P.; Yip, C.C.; Zhang, R.R.; Fung, A.Y.; Yan, E.Y.; Leung, K.H.; Ip, J.D.; Chu, A.W.; Chan, W.M.; Ng, A.C.; Lee, R.; Fung, K.; Yeung, A.; Wu, T.C.; Chan, J.W.; Yan, W.W.; Chan, W.M.; Chan, J.F.; Lie, A.K.; Tsang, O.T.; Cheng, V.C.; Que, T.L.; Lau, C.S.; Chan, K.H.; To, K.K.; Yuen, K.Y. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an openlabel, randomised, phase 2 trial. Lancet, 2020, 395(10238), 1695- 1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10. PMID: 32401715; PMCID: PMC7211500.
(c)Guy, R.K.; DiPaola, R.S.; Romaneli, F.R.E. Dutch, rapid re-purposing drugs for COVID-19. Science, 2020, 368(6493), 829-830.
[PMID: 32385101]
(d)Ciliberto, G.; Mancini, R.; Paggi, M.G. Drug repurposing against COVID-19: Focus on anticancer agents. J. Exp. Clin. Cancer Res., 2020, 39(1), 86.
[http://dx.doi.org/10.1186/s13046-020-01590-2] [PMID: 32398164]
[15]
Harper, D. R. Virus Replication. eLS,2012, 1-8.
[http://dx.doi.org/10.1002/9780470015902.a0000438.pub2]
[16]
(a)Hydroxychloroquine Sulfate Monograph for Professionals. The American Society of Health-System Pharmacists., 2020.https://www.drugs.com/monograph/hydroxychloroquine.html
(b)World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva; World Health Organization: , 2019.
[18]
(a)Coronavirus disease 2019. COVID-19. In; Centers for Disease Control and Prevention, 2019.
(b)Schrezenmeier, E.; Dörner, T. Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology. Nat. Rev. Rheumatol., 2020, 16(3), 155-166.
[http://dx.doi.org/10.1038/s41584-020-0372-x] [PMID: 32034323]
[19]
(a)Kalil, A.C. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA, 2020, 323(19), 1897-1898.
[http://dx.doi.org/10.1001/jama.2020.4742] [PMID: 32208486]
(b)NIH clinical trial of hydroxychloroquine, a potential therapy for COVID-19, begins National Institutes of Health (NIH),
(c)Outcomes related to COVID-19 treated With hydroxychloroquine among in-patients With symptomatic disease (ORCHID)
[20]
(a)Surrey, A.R.U.S. Pat. 2.546.658, 1951.
(b)Surrey, A.R.; Hammer, H.F. The preparation of 7-chloro-4-(4-(N-ethyl-N-β-hydroxyethylamino)-1-methylbutylamino)- quinoline and related compounds. J. Am. Chem. Soc., 1950, 72, 1814.
[http://dx.doi.org/10.1021/ja01160a116]
[21]
Yu, E.; Mangunuru, H.P.R.; Telang, N.S.; Kong, C.J.; Verghese, J.; Gilliland Iii, S.E.; Ahmad, S.; Dominey, R.N.; Gupton, B.F. High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine. Beilstein J. Org. Chem., 2018, 14, 583-592.
[http://dx.doi.org/10.3762/bjoc.14.45] [PMID: 29623120]
[22]
Wang, M.Z.; Cai, B.Q.; Li, L.Y. Efficacy and safety of arbidol in treatment of naturally acquired influenza. Acta Academiae Medicinae Sinicae, 2004, 26, 289‐293; b) Y. S. Boriskin, I. A. Leneva, E. I. Pécheur, S. J. Polyak. Arbidol: A broad-spectrum antiviral compound that blocks viral fusión. Curr. Med. Chem., 2008, 15, 997-1005.
[23]
Leneva, I.A.; Russell, R.J.; Boriskin, Y.S.; Hay, A.J. Characteristics of arbidol-resistant mutants of influenza virus: Implications for the mechanism of anti-influenza action of arbidol. Antiviral Res., 2009, 81(2), 132-140.
[http://dx.doi.org/10.1016/j.antiviral.2008.10.009] [PMID: 19028526]
[24]
FDA Approved Drugs for Influenza U.S. Food and Drug Administration. 2012.
[25]
Blaising, J.; Polyak, S.J.; Pécheur, E.I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res., 2014, 107, 84-94.
[http://dx.doi.org/10.1016/j.antiviral.2014.04.006] [PMID: 24769245]
[26]
ClinicalTrials.gov. Identifier NCT04286503., Bethesda (MD): National Library of Medicine (US) The clinical study of carrimycin on treatment patients with Covid-19., , 2020.
[27]
ClinicalTrials.gov. Identifier NCT04260594., Bethesda (MD): National Library of Medicine. US; Clinical Study of Arbidol Hydrochloride Tablets in the Treatment of Pneumonia Caused by Novel Coronavirus, 2020.
[28]
(a)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]
(b)National Center for Biotechnology Information. PubChem Compound Summary for CID 131411, Arbidol, https://pubchem.ncbi.nlm.nih.gov/compound/Arbidol
[29]
(a)Trofimov, F.A.; Tsyshkova, N.G.; Zotova, S.A. Synthesis of a new antiviral agent, arbidole. Pharm. Chem. J., 1993, 27, 75-76.,
[http://dx.doi.org/10.1007/BF00772858]
(b)Bhakat, S.; Soliman, M.E. Chikungunya virus (CHIKV) inhibitors from natural sources: a medicinal chemistry perspective. J. Nat. Med., 2015, 69(4), 451-462.
[http://dx.doi.org/10.1007/s11418-015-0910-z] [PMID: 25921858]
[30]
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; and Ray, A.S. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 2018, 9(2)
[http://dx.doi.org/10.1128/mBio.00221-18]
[34]
Sheahan, T.P.; Sims, A.C.; Graham, R.L. Sci. Transl. Med., 2017, 9, l3653.
[http://dx.doi.org/10.1126/scitranslmed.aal3653]
[35]
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]
[36]
Okuhira, K.; Shoda, T.; Omura, R.; Ohoka, N.; Hattori, T.; Shibata, N.; Demizu, Y.; Sugihara, R.; Ichino, A.; Kawahara, H.; Itoh, Y.; Ishikawa, M.; Hashimoto, Y.; Kurihara, M.; Itoh, S.; Saito, H.; Naito, M. Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules. Mol. Pharmacol., 2017, 91(3), 159-166.
[http://dx.doi.org/10.1124/mol.116.105569] [PMID: 27965304]
[38]
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]
[39]
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, 17-21.
[http://dx.doi.org/10.1016/j.antiviral.2014.02.014] [PMID: 24583123]
[40]
Du, Y.X.; Chen, X.P. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin. Pharmacol. Ther., 2020 Aug, 108(2), 242-247.
[http://dx.doi.org/10.1002/cpt.1844] [PMID: 32246834.]
[41]
Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov., 2020, 19(3), 149-150.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[42]
Brief –Corrected – Zhejiang Hisun Pharma gets approval for clinical trial to test flu drug Favipiravir for pneumonia caused by new coronavirus. Reuters Healthcare, 2020.https://fr.reuters.com/article/idUKL4N2AH0C8
[43]
Fujifilm Announces the Start of a Phase III Clinical Trial of Influenza Antiviral Drug Avigan (favipiravir) on COVID-19 in Japan and Commits to Increasing Production https://www.fujifilm.com/jp/en/news/hq/3211
[44]
Coronavirus, il Veneto sperimenta l'antivirale giapponese Favipiravir. Ma l'Aifa: "Ci sono scarse evidenze scientifiche su efficacia https://www.ilfattoquotidiano.it/2020/03/22/coronavirus-il-veneto-sperimenta-lantivirale-giapponese-favipiravir-ma-laifa-ci-sono-scarse-evidenze-scientifiche-su-efficacia/5745426/
[45]
AIFA precisa, uso favipiravir per COVID-19 non autorizzato in Europa e USA, scarse evidenze scientifiche sull’efficacia aifa. aifa.gov.it
[46]
Furuta, Y.; Egawa, H.; Int, P.C.T. Appl. WO2000010569A1. Chem. Abstr., 2000.132194392
[47]
Qi, G.; Mingshuo, X.; Shuang, G.; Fuqiang, Z.; Yuanchao, X.; Jingshan, S. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. Pap., 2019, 73, 1043-1051.
[http://dx.doi.org/10.1007/s11696-018-0654-9]
[48]
Robert, W.M.; Peter, C.T.; Gary, B.E.; Richard, H.F.; David, W.P.; Vern, L.S. Iminoribitol Transition State Analogue Inhibitors of Protozoan Nucleoside Hydrolases. Biochemistry, 1999, 38, 13147-13154.
[http://dx.doi.org/10.1021/bi990829u] [PMID: 10529186]
[49]
Warren, T.K.; Wells, J.; Panchal, R.G.; Stuthman, K.S.; Garza, N.L.; Van Tongeren, S.A.; Dong, L.; Retterer, C.J.; Eaton, B.P.; Pegoraro, G.; Honnold, S.; Bantia, S.; Kotian, P.; Chen, X.; Taubenheim, B.R.; Welch, L.S.; Minning, D.M.; Babu, Y.S.; Sheridan, W.P.; Bavari, S. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature, 2014, 508(7496), 402-405.
[http://dx.doi.org/10.1038/nature13027] [PMID: 24590073]
[51]
Kunisuke, I.; José Luis, A.; Jiang, W.; Vadim, A.S.; Hong, L. Small-Molecule Therapeutics for Ebola Virus (EBOV) Disease Treatment. Eur. J. Org. Chem., 2016, 1, 8-16.
[52]
Eli Lilly and Company. FDA approves Olumiant (baricitinib) 2-mg tablets for the treatment of adults with moderately-to-severely active rheumatoid arthritis 2018.
[53]
Drug Trials Snapshots. Olumiant U.S. Food and Drug Administration; FDA, 2018.
[54]
Olumiant, EPAR 2019.
[55]
Drug Approval Package : Olumiant (baricitini. 2018.
[57]
Kobierski, M. E.; Kopach, M. E.; Martinelli, J. R.; Varie, D. L.; Wilson, T. M. WO 2016/205487, 2016.
[58]
Hughes, D.L. Applications of Flow Chemistry in Drug Development: Highlights of Recent Patent Literature. Org. Process Res. Dev., 2018, 22, 13-20.
[http://dx.doi.org/10.1021/acs.oprd.7b00363]
[59]
Mesa, R.A.; Yasothan, U.; Kirkpatrick, P. Ruxolitinib. Nat. Rev. Drug Discov., 2012, 11(2), 103-104.
[http://dx.doi.org/10.1038/nrd3652] [PMID: 22293561]
[60]
Harrison, C.; Mesa, R.; Ross, D.; Mead, A.; Keohane, C.; Gotlib, J.; Verstovsek, S. Practical management of patients with myelofibrosis receiving ruxolitinib. Expert Rev. Hematol., 2013, 6(5), 511-523.
[http://dx.doi.org/10.1586/17474086.2013.827413] [PMID: 24083419]
[61]
] Incyte Announces Plans to Initiate a Phase 3 Clinical Trial of Ruxolitinib (Jakafi) as a Treatment for Patients with COVID-19 Associated Cytokine Storm. 2020.
[63]
US2007135461A1/ US7598257B2; WO2010039939A1; WO2013023119A1, 2012.
[64]
Habibi, M.; Kuttab, H.M. Management of multiple sclerosis and the integration of related specialty pharmacy programs within health systems. Am. J. Health Syst. Pharm., 2016, 73(11), 811-819.
[http://dx.doi.org/10.2146/ajhp150723] [PMID: 27126827]
[65]
(a)Reddy, EK; Remya, C; Mantosh, K; Sajith, AM; Omkumar, RV; Sadasivan, C; Anwar, S S. Novel tacrine derivatives exhibiting improved acetylcholinesterase inhibition: Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2017, 139, 367-377. doi: 10.1016/j.ejmech.2017.08.013. Epub 2017 Aug 5. PMID: 28810188.,
[http://dx.doi.org/10.1016/j.ejmech.2017.08.013] [PMID: 28810188]
(b)Reddy, E.K.; Chandran, R.; Sajith, A.M.; Dileep, K.V.; Sadasivan, C.; Anwar, S. Functionalised dihydroazo pyrimidine derivatives from Morita–Baylis–Hillman acetates: synthesis and studies against acetylcholinesterase as its inhibitors. RSC Adv, 2016, 6, 77431-77439.
[http://dx.doi.org/10.1039/C6RA12507G]
[66]
Noseworthy, J.H.; Lucchinetti, C.; Rodriguez, M.; Weinshenker, B.G. Multiple sclerosis. N. Engl. J. Med., 2000, 343(13), 938-952.
[http://dx.doi.org/10.1056/NEJM200009283431307] [PMID: 11006371]
[68]
Naveen, M. A Comprehensive Review on Synthetic Approach for Fingolimod. Indian J. Adv. Chem. Sci., 2016, 4, 362-366.
[69]
Thalidomide Monograph for Professionals. 2012.https://www.drugs.com/monograph/thalidomide.html
[70]
The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19). Pneumonia, 2012.
[71]
Muller, G.W.; Konnecke, W.E.; Smith, A.M.; Khetani, V.D. A Concise Two-Step Synthesis of Thalidomide. Org. Process Res. Dev., 1999, 3, 139-140.
[http://dx.doi.org/10.1021/op980201b]
[72]
Vu, B.D.; Ho Ba, N.M.; Phan, D.C. Facile Synthesis of Thalidomide. Org. Process Res. Dev., 2019, 23, 1374-1377.
[http://dx.doi.org/10.1021/acs.oprd.9b00122]
[73]
Busse, K.H.S.; Penzak, S.R. Darunavir: a second-generation protease inhibitor. Am. J. Health Syst. Pharm., 2007, 64(15), 1593-1602.
[http://dx.doi.org/10.2146/ajhp060668] [PMID: 17646561]
[74]
Prezista- darunavir tablet, film coated Prezista- darunavir suspension https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=814301f9-c990-46a5-b481-2879a521a16f
[76]
Moore, G.L.; Stringham, R.W.; Teager, D.S.; Yue, T-Y. Practical Synthesis of the Bicyclic Darunavir Side Chain: (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol from Monopotassium Isocitrate. Org. Process Res. Dev., 2017, 21(1), 98-106.
[http://dx.doi.org/10.1021/acs.oprd.6b00377] [PMID: 28539755]
[77]
Kanemitsu, T.; Inoue, M.; Yoshimura, N.; Yoneyama, K.; Watarai, R.; Miyazaki, M.; Odanaka, Y.; Nagata, K.; Itoh, T. A concise one‐pot organo‐ and biocatalyzed preparation of enantiopure Hexahydrofuro[2,3‐b]furan‐3‐ol: An approach to the synthesis of HIV protease inhibitors. Eur. J. Org. Chem., 2016, 1874-1880.
[http://dx.doi.org/10.1002/ejoc.201600062]
[78]
Agostini, M.L.; Pruijssers, A.J.; Chappell, J.D.; Gribble, J.; Lu, X.; Andres, E.L.; Bluemling, G.R.; Lockwood, M.A.; Sheahan, T.P.; Sims, A.C.; Natchus, M.G.; Saindane, M.; Kolykhalov, A.A.; Painter, G.R.; Baric, R.S.; Denison, M.R. Small-Molecule antiviral β-d-N4-Hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance. J. Virol., 2019, 93(24), e01348-e19.
[http://dx.doi.org/10.1128/JVI.01348-19] [PMID: 31578288]
[81]
(a)Toots, M.; Yoon, J.J.; Cox, R.M.; Hart, M.; Sticher, Z.M.; Makhsous, N.; Plesker, R.; Barrena, A.H.; Reddy, P.G.; Mitchell, D.G.; Shean, R.C.; Bluemling, G.R.; Kolykhalov, A.A.; Greninger, A.L.; Natchus, M.G.; Painter, G.R.; Plemper, R.K. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci. Transl. Med., 2019, 11(515), eaax5866.,
[http://dx.doi.org/10.1126/scitranslmed.aax5866] [PMID: 31645453]
(b)Sheahan, T.P.; Sims, A.C.; Zhou, S.; Graham, R.L.; Pruijssers, A.J.; Agostini, M.L.; Leist, S.R.; Schäfer, A.; Dinnon, K.H., III; Stevens, L.J.; Chappell, J.D.; Lu, X.; Hughes, T.M.; George, A.S.; Hill, C.S.; Montgomery, S.A.; Brown, A.J.; Bluemling, G.R.; Natchus, M.G.; Saindane, M.; Kolykhalov, A.A.; Painter, G.; Harcourt, J.; Tamin, A.; Thornburg, N.J.; Swanstrom, R.; Denison, M.R.; Baric, R.S. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med., 2020, 12(541)eabb5883
[http://dx.doi.org/10.1126/scitranslmed.abb5883] [PMID: 32253226]
[82]
Yoon, J.J.; Toots, M.; Lee, S.; Lee, M.E.; Ludeke, B.; Luczo, J.M.; Ganti, K.; Cox, R.M.; Sticher, Z.M.; Edpuganti, V.; Mitchell, D.G.; Lockwood, M.A.; Kolykhalov, A.A.; Greninger, A.L.; Moore, M.L.; Painter, G.R.; Lowen, A.C.; Tompkins, S.M.; Fearns, R.; Natchus, M.G.; Plemper, R.K. Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses. Antimicrob. Agents Chemother., 2018, 62(8), e00766-e18.
[http://dx.doi.org/10.1128/AAC.00766-18] [PMID: 29891600]
[83]
FDA clears the way for ridgeback biotherapeutics to begin human testing of a promising potential treatment for COVID-19 2020.https://www.prnewswire.com/news-releases/fda-clears-the-way-for-ridgeback-biotherapeutics-to-begin-human-testing-of-a-promising-potential-treatment-for-covid-19-301036307.html
[84]
Painter, G. R.; Perryman, D.; Bluemling, G. R. WO2019173602 - 4'-halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto; PCT Int. Appl. WO 2019173602 A1 20190912., 2019. 2019.
[85]
(a)Azzariti, A.; Colabufo, N.A.; Berardi, F.; Porcelli, L.; Niso, M.; Simone, G.M.; Perrone, R.; Paradiso, A. Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer. Mol. Cancer Ther., 2006, 5(7), 1807-1816.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0402] [PMID: 16891467]
(b)Abate, C.; Elenewski, J.; Niso, M.; Berardi, F.; Colabufo, N.A.; Azzariti, A.; Perrone, R.; Glennon, R.A. Interaction of the sigma(2) receptor ligand PB28 with the human nucleosome: Computational and experimental probes of interaction with the H2A/H2B dimer. ChemMedChem, 2010, 5(2), 268-273.
[http://dx.doi.org/10.1002/cmdc.200900402] [PMID: 20077462]
[87]
Gordon, D.E.; Jang, G.M.; Bouhaddou, M.; Xu, J.; Obernier, K.; White, K.M.; O’Meara, M.J.; Rezelj, V.V.; Guo, J.Z.; Swaney, D.L.; Tummino, T.A.; Hüttenhain, R.; Kaake, R.M.; Richards, A.L.; Tutuncuoglu, B.; Foussard, H.; Batra, J.; Haas, K.; Modak, M.; Kim, M.; Haas, P.; Polacco, B.J.; Braberg, H.; Fabius, J.M.; Eckhardt, M.; Soucheray, M.; Bennett, M.J.; Cakir, M.; McGregor, M.J.; Li, Q.; Meyer, B.; Roesch, F.; Vallet, T.; Mac Kain, A.; Miorin, L.; Moreno, E.; Naing, Z.Z.C.; Zhou, Y.; Peng, S.; Shi, Y.; Zhang, Z.; Shen, W.; Kirby, I.T.; Melnyk, J.E.; Chorba, J.S.; Lou, K.; Dai, S.A.; Barrio-Hernandez, I.; Memon, D.; Hernandez-Armenta, C.; Lyu, J.; Mathy, C.J.P.; Perica, T.; Pilla, K.B.; Ganesan, S.J.; Saltzberg, D.J.; Rakesh, R.; Liu, X.; Rosenthal, S.B.; Calviello, L.; Venkataramanan, S.; Liboy-Lugo, J.; Lin, Y.; Huang, X.P.; Liu, Y.; Wankowicz, S.A.; Bohn, M.; Safari, M.; Ugur, F.S.; Koh, C.; Savar, N.S.; Tran, Q.D.; Shengjuler, D.; Fletcher, S.J.; O’Neal, M.C.; Cai, Y.; Chang, J.C.J.; Broadhurst, D.J.; Klippsten, S.; Sharp, P.P.; Wenzell, N.A.; Kuzuoglu-Ozturk, D.; Wang, H.Y.; Trenker, R.; Young, J.M.; Cavero, D.A.; Hiatt, J.; Roth, T.L.; Rathore, U.; Subramanian, A.; Noack, J.; Hubert, M.; Stroud, R.M.; Frankel, A.D.; Rosenberg, O.S.; Verba, K.A.; Agard, D.A.; Ott, M.; Emerman, M.; Jura, N.; von Zastrow, M.; Verdin, E.; Ashworth, A.; Schwartz, O.; d’Enfert, C.; Mukherjee, S.; Jacobson, M.; Malik, H.S.; Fujimori, D.G.; Ideker, T.; Craik, C.S.; Floor, S.N.; Fraser, J.S.; Gross, J.D.; Sali, A.; Roth, B.L.; Ruggero, D.; Taunton, J.; Kortemme, T.; Beltrao, P.; Vignuzzi, M.; García-Sastre, A.; Shokat, K.M.; Shoichet, B.K.; Krogan, N.J.A. SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 2020, 583(7816), 459-468.
[http://dx.doi.org/10.1038/s41586-020-2286-9] [PMID: 32353859]
[88]
Abate, Carmen Carmen Abate,; Francesco Berardi,; Nicola Antonio Colabufo,; Savina Ferorelli,; Roberto Perrone; Tritium radiolabeling of [3h]-1- cyclohexyl-4-[3-(5-methoxy-1,2, 3,4,-tetrahydronaphthalen-1-yl)- n-propyl]piperazine ([3h]-pb28), as a potent sigma-2 receptor ligand. From PCT Int.. 2009, 104058. 2009.
[89]
(a)Corbett, A.H.; Lim, M.L.; Kashuba, A.D. Kaletra (lopinavir/ritonavir). Ann. Pharmacother., 2002, 36(7-8), 1193-1203. 2002.
[http://dx.doi.org/10.1345/aph.1A363] [PMID: 12086554]
(b)Approved Drug Products, FDA
[90]
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.
[PMID: 32187464; PMCID: PMC7121492.] [http://dx.doi.org/10.1056/NEJMoa2001282]
[91]
(a)Eric, J.S.; Arthur, J.C.A.D. Daniel. Synthesis of HIV Protease Inhibitor ABT-378 (Lopinavir). Org. Process Res. Dev., 2000, 4, 264-269.
(b)Ghosh, A.K.; Bilcer, G.; Schiltz, G. Syntheses of FDA Approved HIV Protease Inhibitors. Synthesis (Stuttg), 2001, 2001(15), 2203-2229.
[http://dx.doi.org/10.1055/s-2001-18434] [PMID: 30393404]
[92]
] Pietro Bellani,; Marco Frigerio,; Patrizia Castoldi; Process for the synthesis of ritonavir; US6407252B1 2001.
[93]
BELLANI. Pietro; FRIGERIO, Marco; CASTOLDI, Patrizia a process for the synthesis of ritonavir; WO2001021603A1 2016.
[94]
Liu, J.; Zheng, X.; Tong, Q.; Li, W.; Wang, B.; Sutter, K.; Trilling, M.; Lu, M.; Dittmer, U.; Yang, D. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J. Med. Virol., 2020, 92(5), 491-494.
[http://dx.doi.org/10.1002/jmv.25709] [PMID: 32056249]
[95]
Habib, A.M.G.; Ali, M.A.E.; Zouaoui, B.R.; Taha, M.A.H.; Mohammed, B.S.; Saquib, N. Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. BMC Infect. Dis., 2019, 19(1), 870.
[http://dx.doi.org/10.1186/s12879-019-4555-5] [PMID: 31640578]
[96]
Peiris, J.S.; Chu, C.M.; Cheng, V.C.; Chan, K.S.; Hung, I.F.; Poon, L.L.; Law, K.I.; Tang, B.S.; Hon, T.Y.; Chan, C.S.; Chan, K.H.; Ng, J.S.; Zheng, B.J.; Ng, W.L.; Lai, R.W.; Guan, Y.; Yuen, K.Y. HKU/UCH SARS Study Group. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet, 2003, 361(9371), 1767-1772.
[http://dx.doi.org/10.1016/S0140-6736(03)13412-5] [PMID: 12781535]
[97]
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]
[98]
Graci, J.D.; Cameron, C.E. Mechanisms of action of ribavirin against distinct viruses. Rev. Med. Virol., 2006, 16(1), 37-48.
[http://dx.doi.org/10.1002/rmv.483] [PMID: 16287208]
[99]
Crotty, S.; Cameron, C.E.; Andino, R. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6895-6900.
[http://dx.doi.org/10.1073/pnas.111085598] [PMID: 11371613]
[100]
Khalili, J.S.; Zhu, H.; Mak, N.S.A.; Yan, Y.; Zhu, Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J. Med. Virol., 2020, 92(7), 740-746.
[http://dx.doi.org/10.1002/jmv.25798] [PMID: 32227493]
[101]
Witkowski, J.T.; Robins, R.K.; Frank, A.L. U.S. Pat. 3.976.545, 1976. 5-Hydroxyl-1,2,3-triazole-4-carboxamide nucleoside; US3948885A
[102]
L. Christensen, ; J.T. Witkowski, U.S. Pat. 4.138.547 1979.
[103]
Witkowski, J.T.; Robins, R.K.; Sidwell, R.W.; Simon, L.N. Design, synthesis, and broad spectrum antiviral activity of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. J. Med. Chem., 1972, 15(11), 1150-1154.
[http://dx.doi.org/10.1021/jm00281a014] [PMID: 4347550]
[104]
Witkowski, J.T.; Christensen, L.F.; Robins, R.K. Carbohyd. Chemistry of Nucleosides and Nucleotides. J. Nucl. Nucl., 1978, 5, 363.
[105]
Ito, Y.; Nii, Y.; Kobayashi, S.; Ohno, M. Regioselective synthesis of virazole using benzyl cyanoformate as a synthon. Tetrahedron Lett., 1979, 20, 2521.
[http://dx.doi.org/10.1016/S0040-4039(01)86338-3]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy