Ten paths to the discovery of antivirally active nucleoside and nucleotide analogues

Nucleosides, Nucleotides and Nucleic Acids

Volumn 31, Issue 4, 2012, Pages 339-352

  De Clercq, Erik ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

adenosine receptor ligands; anticancer nucleosides; Antiviral nucleosides

Indexed keywords

3 DEAZAARISTEROMYCIN; 3 DEAZANEPLANOCIN A; 5 (2 BROMOVINYL) 2' DEOXYURIDINE; 9 (2,3 DIHYDROXYPROPYL)ADENINE; 9 (3 HYDROXY 2 PHOSPHONOMETHOXYPROPYL)ADENINE; ACICLOVIR; ADEFOVIR DIPIVOXIL; ANTIVIRUS AGENT; BRIVIRAC; CIDOFOVIR; EFAVIRENZ PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; EMTRICITABINE PLUS RILPIVIRINE PLUS TENOFOVIR DISOPROXIL; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; FERMAVIR; FV 100; NEPLANOCIN A; NUCLEOSIDE; NUCLEOSIDE DERIVATIVE; NUCLEOTIDE DERIVATIVE; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; VALACICLOVIR; ZERPEX; ZOSTEX;

ADENOVIRUS; ANTIVIRAL ACTIVITY; ARTICLE; CYTOMEGALOVIRUS RETINITIS; DNA VIRUS INFECTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG SYNTHESIS; EBOLA VIRUS; ENZYME PHOSPHORYLATION; GEL; GENITAL HERPES; HEMORRHAGIC FEVER; HEPATITIS B; HERPES LABIALIS; HERPES SIMPLEX KERATITIS; HERPES SIMPLEX VIRUS; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HERPES VIRUS INFECTION; HERPES ZOSTER; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; KERATITIS; MALE HOMOSEXUAL; NONHUMAN; POXVIRUS; POXVIRUS INFECTION; RHABDOVIRUS; TREATMENT DURATION; VACCINATION; VARICELLA ZOSTER VIRUS; VESICULAR STOMATITIS VIRUS; VIRUS INHIBITION;

ANTIVIRAL AGENTS; DRUG DISCOVERY; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; NUCLEOSIDES; NUCLEOTIDES;

EID: 84859173660     PISSN: 15257770     EISSN: 15322335     Source Type: Journal    
DOI: 10.1080/15257770.2012.657383     Document Type: Article

References (61)

1. De Clercq, E.; Descamps, J.; De Somer, P.; Holy, A. (S)-9-(2,3- Dihydroxypropyl)-adenine: an aliphatic nucleoside analog with broad spectrum antiviral activity. Science 1978, 200, 563-565.
2. De Clercq, E. S-Adenosylhomocysteine hydrolase inhibitors as broad-spectrum antiviral agents. Biochem. Pharmacol. 1987, 36, 2567-2575.
3. Elion, G.B.; Furman, P.A.; Fyfe, J.A.; de Miranda, P.; Beauchamp, L.; Schaeffer, H.J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. USA 1977, 74, 5716-5720.
4. Schaeffer, H.J.; Beauchamp, L.; de Miranda, P.; Elion, G.B.; Bauer, D.J.; Collins, P. 9-(2-Hydroxyethoxymethyl)guanine activity against viruses of the herpes group. Nature 1978, 272, 583-585.
5. Montgomery, J.A.; Clayton, S.J.; Thomas, H.J.; Shannon, W.M.; Arnett, G.; Bodner, A.J.; Kion, I.K.; Cantoni, G.L.; Chiang, P.K. Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target. J. Med. Chem. 1982, 25, 626-629.
6. De Clercq, E. John Montgomery's legacy: carbocyclic adenosine analogues as SAH hydrolase inhibitors with broad-spectrum antiviral activity. Nucleosides, Nucleotides & Nucleic Acids 2005, 24, 1395-1415.
7. De Clercq, E.; Montgomery, J.A. Broad-spectrum antiviral activity of the carbocyclic analog of 3-deazaadenosine. Antiviral Res. 1983, 3, 17-24.
8. De Clercq, E.; Bergstrom, D.E.; Holy, A.; Montgomery, J.A. Broad-spectrum antiviral activity of adenosine analogues. Antiviral Res. 1984, 4, 119-133.
9. De Clercq, E.; Descamps, J.; De Somer, P.; Barr, P.J.; Jones, A.S.; Walker, R.T. E-5-(2-Bromovinyl)-2′-deoxyuridine: a potent and selective antiherpes agent. Proc. Natl. Acad. Sci. USA 1979, 76, 2947-2951.
10. De Clercq, E. Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster. Biochem. Pharmacol. 2004, 68, 2301-2315.
11. De Clercq, E. The antiviral spectrum of (E)-5-(2-bromovinyl)-2′- deoxyuridine. J. Antimicrob. Chemother. 1984, 14(Suppl. A), 85-95.
12. De Clercq, E.; Degreef, H.; Wildiers, J.; De Jonge, G.; Drochmans, A.; Descamps, J.; De Somer, P. Oral (E)-5-(2-bromovinyl)-2′-deoxyuridine in severe herpes zoster. Brit. Med. J. 1980, 281, 1178.
13. Maudgal, P.C.; De Clercq, E.; Descamps, J.; Missotten, L.; De Somer, P., Busson, R.; Vanderhaeghe, H.; Verhelst, G.; Walker, R.T.; Jones, A.S. (E)-5-(2-Bromovinyl)-2′-deoxyuridine in the treatment of experimental herpes simplex keratitis. Antimicrob. Agents Chemother. 1980, 17, 8-12.
14. Maudgal, P.C.; Missotten, L.; De Clercq, E.; Descamps, J.; De Meuter, E. Efficacy of (E)-5-(2-bromovinyl)-2′-deoxyuridine in the topical treatment of herpes simplex keratitis. Albrecht von Graefes Arch. Klin. Ophthalmol. 1981, 216, 261-268.
15. Maudgal, P.C.; De Clercq, E.; Descamps, J.; Missotten, L.; Wijhoven, J. Experimental stromal herpes simplex keratitis. Influence of treatment with topical bromovinyldeoxyuridine and trifluridine. Arch. Ophthalmol. 1982, 100, 653-656.
16. Maudgal, P.C.; Uyttebroeck, W.; De Clercq, E.; Missotten, L. Oral and topical treatment of experimental herpes simplex iritis with bromovinyldeoxyuridine. Arch. Ophthalmol. 1982, 100, 1337-1340.
17. Maudgal, P.C.; De Clercq, E.; Missotten, L. Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections. Antiviral Res. 1984, 4, 281-291.
18. Beauchamp, L.M.; Orr, G.F.; de Miranda, P.; Burnette, T.; Krenitsky, T.A. Amino acid ester prodrugs of acyclovir. Antiviral Chem. Chemother. 1992, 3, 157-164.
19. Colla, L.; De Clercq, E.; Busson, R.; Vanderhaeghe, H. Synthesis and antiviral activity of water-soluble esters of acyclovir [9-(2- hydroxyethoxymethyl)guanine]. J. Med. Chem. 1983, 26, 602-604.
20. Maudgal, P.C.; De Clercq, E.; Descamps, J.; Missotten, L. Topical treatment of experimental herpes simplex keratouveitis with 2′-O- glycylacyclovir. A water-soluble ester of acyclovir. Arch. Ophthalmol. 1984, 102, 140-142.
21. De Clercq, E.; Holy, A.; Rosenberg, I.; Sakuma, T.; Balzarini, J.; Maudgal, P.C. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986, 323, 464-467.
22. Stittelaar, K.J.; Neyts, J.; Naesens, L.; van Amerongen, G.; van Lavieren, R.F.; Holy, A.; De Clercq, E.; Niesters, H.G.; Fries, E.; Maas, C; Mulder, P.G.; van der Zeijst, B.A.; Osterhaus, A.D. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature 2006, 439, 745-748.
23. Hostetler, K.Y. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antiviral Res. 2009, 82, A84-A98.
24. Pauwels, R.; Balzarini, J.; Schols, D.; Baba, M.; Desmyter, J.; Rosenberg, I.; Holy, A.; De Clercq, E. Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents. Antimicrob. Agents Chemother. 1988, 32, 1025-1030.
25. De Clercq, E.; Sakuma, T.; Baba, M.; Pauwels, R.; Balzarini, J.; Rosenberg, I.; Holy, A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res. 1987, 8, 261-272.
26. Balzarini, J.; Holy, A.; Jindrich, J.; Naesens, L.; Snoeck, R.; Schols, D.; De Clercq, E. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2- phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob. Agents Chemother. 1993, 37, 332-338.
27. De Clercq, E. Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections. Expert Rev Anti-Infect. Ther. 2003, 1, 21-43.
28. Cihlar, T.; Delaney IV, W.E.; Mackman, R. Tenofovir and adefovir as antiviral agents, in Modified Nucleosides in Biochemistry, Biotechnology and Medicine, ed. P. Herdewijn, Wiley-VCH Verlag, Weinheim, Germany, 2008, pp. 601-630.
29. De Clercq, E. From adefovir to Atripla via tenofovir, Viread and Truvada. Future Virol. 2006, 1, 709-715.
30. Tsai, C.-C; Follis, K.E.; Sabo, A.; Beck, T.W.; Grant, R.F.; Bischofberger, N.; Benveniste, R.E.; Black, R. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science 1995, 270, 1197-1198.
31. Willyard, C. A preemptive strike against HIV. Nat. Med. 2009, 15, 126-129.
32. Abdool Karim, S.S.; Baxter, C. Antiretroviral prophylaxis for the prevention of HIV infection: future implementation challenges. HIVTher. 2009, 3, 3-6.
33. Abdool Karim, Q.; Abdool Karim, S.S.; Frohlich, J.A.; Grobler, A.C.; Baxter, C; Mansoor, L.E.; Kharsany, A.B.; Sibeko, S.; Mlisana, K.P.; Omar, Z.; Gengiah, T.N.; Maarschalk, S.; Arulappan, N.; Mlotshwa, M.; Morris, L.; Taylor, D.; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010, 329, 1168-1174.
34. Grant, R.M.; Lama, J.R.; Anderson, P.L.; McMahan, V.; Liu, A.Y.; Vargas, L.; Goicochea, P.; Casapía, M.; Guanira-Carranza, J.V.; Ramirez-Cardich, M.E.; Montoya-Herrera, O.; Fernandez, T.; Veloso, V.G.; Buchbinder, S.P.; Chariyalertsak, S.; Schechter, M.; Bekker, L.G.; Mayer, K.H.; Kallas, E.G.; Amico, K.R.; Mulligan, K.; Bushman, L.R.; Hance, R.J.; Ganoza, C; Defechereux, P.; Postle, B.; Wang, F.; McConnell, J.J.; Zheng, J.H.; Lee, J.; Rooney, J.F.; Jaffe, H.S.; Martinez, A.I.; Burns, D.N.; Glidden, D.V.; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 2010, 363, 2587-2599.
35. McGuigan, C; Barucki, H.; Blewett, S.; Carangio, A.; Erichsen, J.T.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J. Highly potent and selective inhibition of varicella-zoster virus by bicyclic furopyrimidine nucleosides bearing an aryl side chain. J. Med. Chem. 2000, 43, 4993-4997.
36. Andrei, G.; Sienaert, R.; McGuigan, C.; De Clercq, E.; Balzarini, J.; Snoeck, R. Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides. Antimicrob. Agents Chemother. 2005, 49, 1081-1086.
37. De Clercq, E. Highly potent and selective inhibition of varicella-zoster virus replication by bicyclic furo[2,3-d]pyrimidine nucleoside analogues. Med. Res. Rev. 2003, 23, 253-274.
38. McGuigan, C.; Pathirana, R.N.; Migliore, M.; Adak, R.; Luoni, G.; Jones, A.T.; Diez-Torrubia, A.; Camarasa, M.-J.; Velázquez, S.; Henson, G.; Verbeken, E.; Sienaert, R.; Naesens, L.; Snoeck, R.; Andrei, G.; Balzarini, J. Preclinical development of bicyclic nucleoside analogues as potent and selective inhibitors of varicella zoster virus. J. Antimicrob. Chemother. 2007, 60, 1316-1330.
39. De Clercq, E. Antiviral drug discovery: ten more compounds, and ten more stories (part B). Med. Res. Rev. 2009, 29, 571-610.
40. Krečmerová, M.; Holý, A.; Pískala, A.; Masojídková, M.; Andrei, G.; Naesens, L.; Neyts, J.; Balzarini, J.; De Clercq, E.; Snoeck, R. Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]cytosine (cidofovir) and related compounds. J. Med. Chem. 2007, 50, 1068-1077.
41. Holý, A.; Votruba, I.; Masojídková, M.; Andrei, G.; Snoeck, R.; Naesens, L.; De Clercq, E.; Balzarini, J. 6-[2-(Phosphonomethoxy) alkoxy]pyrimidines with antiviral activity. J. Med. Chem. 2002, 45, 1918-1929.
42. Hocková, D.; Holý, A.; Masojídková, M.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J. 5-Substituted-2,4-diamino- 6-[2-(phosphonomethoxy)ethoxy]pyrimi-dines-acyclic nucleoside phospho-nate analogues with antiviral activity. J. Med. Chem. 2003, 46, 5064-5073.
43. Hocková, D.; Holý, A.; Masojídková, M.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J. Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds. Bioorg. Med. Chem. 2004, 12, 3197-3202.
44. De Clercq, E.; Andrei, G.; Balzarini, J.; Leyssen, P.; Naesens, L.; Neyts, J.; Pannecouque, C.; Snoeck, R.; Ying, C.; Hocková, D.; Holý, A. Antiviral potential of a new generation of acyclic nucleoside phos-phonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines. Nucleosides, Nucleotides & Nucleic Acids 2005, 24, 331-341.
45. Naesens, L.; Andrei, G.; Votruba, I.; Krečmerová, M.; Holý, A.; Neyts, J.; De Clercq, E.; Snoeck, R. Intra-cellular metabolism of the new antiviral compound 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5- azacytosine. Biochem. Pharmacol. 2008, 76, 997-1005.
46. Wu, T.; Froeyen, M.; Kempeneers, V.; Pannecouque, C.; Wang, J.; Busson, R.; De Clercq, E.; Herdewijn, P. Deoxythreosyl phosphonate nucleosides as selective anti-HIV agents. J. Am. Chem. Soc. 2005, 127, 5056-5065.
47. Kim, C.U.; Luh, B.Y.; Martin, J.C. Regiospecific and highly stereoselective electrophilic addition to furanoid glycals: synthesis of phosphonate nucleotide analogues with potent activity against HIV. J. Org. Chem. 1991, 56, 2642-2647.
48. Cihlar, T.; Ray, A.S.; Boojamra, C.G.; Zhang, L.; Hui, H.; Laflamme, G.; Vela, J.E.; Grant, D.; Chen, J.; Myrick, F.; White, K.L.; Gao, Y.; Lin, K.-Y.; Douglas, J.L.; Parkin, N.T.; Carey, A.; Pakdaman, R.; Mackman, R.L. Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoami-date prodrug, GS-9131. Antimicrob. Agents Chemother. 2008, 52, 655-665.
49. Ray, A.S.; Vela, J.E.; Boojamra, C.G.; Zhang, L.; Hui, H.; Callebaut, C.; Stray, K.; Lin, K.-Y.; Gao, Y.; Mackman, R.L.; Cihlar, T. Intracellular metabolism of the nucleotide prodrug GS-9131, a potent anti-human immunodeficiency virus agent. Antimicrob. Agents Chemother. 2008, 52, 648-654.
50. De Clercq, E. Another ten stories in antiviral drug discovery (part C): "old" and "new" antivirals, strategies, and perspectives. Med. Res. Rev. 2009, 29, 611-645.
51. De Clercq, E. Yet another ten stories on antiviral drug discovery (part D): paradigms, paradoxes, and paraductions. Med. Res. Rev. 2010, 30, 667-707.
52. De Clercq, E. Highlights in the discovery of antiviral drugs: a personal retrospective. J. Med. Chem. 2010, 53, 1438-1450.
53. Cihlar, T.; Ray, A.S. Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Res. 2010, 85, 39-58.
54. De Clercq, E. Discovery and development of tenofovir disoproxil fumarate, in Antiviral Drugs: Biology, Chemistry, Clinic, ed. W.M. Kazmierski, John Wiley & Sons, Hoboken, NJ, 2011, pp. 85-101.
55. Holý, A.; De Clercq, E. Anti-DNA virus agents, in Burger's Medicinal Chemistry, Drug Discovery and Development, 7th ed., ed. D.J. Abraham, D.P. Rotella, John Wiley & Sons, Hoboken, NJ, 2010, pp. 221-258.
56. De Clercq, E. HIV reverse transcriptase inhibitors, in Burger's Medicinal Chemistry, Drug Discovery and Development, 7th ed., ed. D.J. Abraham, D.P. Rotella, John Wiley & Sons, Hoboken, NJ, 2010, pp. 139-168.
57. De Clercq, E. From TIBO to rilpivirine: the chronicle of the discovery of the ideal nonnucleoside reverse transcriptase inhibitor, in Antiviral Drug Strategies, ed. E. De Clercq, "Methods and Principles in Medicinal Chemistry," ed. R. Mannhold, H. Kubinyi, G. Folkers, Wiley-VCH Verlag GmbH, Weinheim, Germany, 2011, pp. 377-389.
58. De Clercq, E. The discovery of antiviral agents: ten different compounds, ten different stories. Med. Res. Rev. 2008, 28, 929-953.
59. De Clercq, E. The next ten stories on antiviral drug discovery (part E): Advents, Advances, and Adventures. Med. Res. Rev. 2011, 31, 118-160.
60. De Clercq, E. Looking back in 2009 at the dawning of antiviral therapy now 50 years ago an historical perspective. Adv. Virus Res. 2009, 73, 1-53.
61. De Clercq, E. A 40-year journey toward the search for a selective antiviral chemotherapy. Annu. Rev. Pharmacol. Toxicol. 2011, 51, 1-24.