Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base

Journal of Medicinal Chemistry

Volumn 42, Issue 12, 1999, Pages 2064-2086

  Holý, Antonín ^a   Günter, Jaroslav ^a   Dvořáková, Hana ^a   Masojídková, Milena ^a   Andrei, Graciela ^b   Snoeck, Robert ^b   Balzarini, Jan ^b   De Clercq, Erik ^b  

^a INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ADEFOVIR; ADEFOVIR DIPIVOXIL; CARBON; CLADRIBINE; FLUDARABINE; PURINE DERIVATIVE; PURINE N [2 (2 PHOSPHONOMETHOXY)ETHYL]; PURINE NUCLEOTIDE; PYRIMIDINE DERIVATIVE; PYRIMIDINE N [2 (2 PHOSPHONOMETHOXY)ETHYL]; PYRIMIDINE NUCLEOTIDE; UNCLASSIFIED DRUG;

ALKYLATION; ANTIVIRAL ACTIVITY; ARTICLE; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ESTERIFICATION; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-HIV AGENTS; ANTIVIRAL AGENTS; CELL LINE; DNA VIRUSES; HIV-1; HIV-2; HUMANS; MOLONEY MURINE SARCOMA VIRUS; PHOSPHONIC ACIDS; PURINE NUCLEOTIDES; PYRIMIDINE NUCLEOTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0345004991     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9811256     Document Type: Article

References (122)

1. (a) De Clercq, E.; Holý, A.; Rosenberg, I.; Sakuma, T.; Baizarini, J.; Maudgal, P. C. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986, 323, 464-467.
2. (b) De Clercq, E.; Sakuma, T.; Baba, M.; Pauwels, R.; Balzarini, J.; Rosenberg, I.; Holý, A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purines and pyrimidines. Antiviral Res. 1987, 8, 261-272.
3. (a) Pauwels, R.; Balzarini, J.; Schols, D.; Baba, M.; Desmyter, P.; Rosenberg, I.; Holý, A.; De Clercq, E. Phosphonylmethoxyethyl purine derivatives: A new class of anti-HIV agents. Antimicrob. Agents Chemother. 1988, 32, 1025-1030.
4. (b) Balzarini, J.; Naesens, L.; Herdewijn, P.; Rosenberg, I.; Holý, A.; Pauwels, R.; Baba, M.; Johns, D. G.; De Clercq, E. Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)-adenine, a selective anti-human immunodeficiency virus agent. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 332-336.
5. (a) Balzarini, J.; Sobis, H.; Naesens, L.; Vandeputte, M.; De Clercq, E. Inhibitory effects of 9-(2-phosphonylmethoxyethyl)-adenine and 3′-azido-2′,3′-dideoxythymidine on tumor development in mice inoculated intracerebrally with Moloney murine sarcoma virus. Int. J. Cancer 1990, 45, 486-489.
6. (b) Balzarini, J.; Naesens, L.; Slachmuylders, J.; Niphuis, H.; Rosenberg, I.; Holý, A.; Schellekens, H.; De Clercq, E. 9-(2-Phosphonylmethoxyethy)adenine (PMEA) effectively inhibits simian immunodeficiency virus (SIV) infection in Rhesus monkeys. AIDS 1991, 5, 21-28.
7. Gangemi, J. D.; Cozens, R. M.; De Clercq, E.; Balzarini, J.; Hochkeppel, H. K. 9-(2-Phosphonylmethoxyethyl)adenme in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections. Antimicrob. Agents Chemother. 1989, 33, 1864-1868.
8. (a) Egberink, H.; Borst, M.; Niphuis, H.; Balzarini, J.; Neu, H.; Schellekens, H.; De Clercq, E.; Horzinek, M.; Koolen, M. Suppression of feline immunodeficiency virus infection in vivo by 9-[2-(phosphonomethoxy)ethyl]adenme. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 3087-3091.
9. (b) Hartmann, K.; Donath, A.; Beer, B.; Egberink, H. F.; Horzinek, M. C.; Lutz, H.; Hoffmann-Fezer, G.; Thum, I.; Thefeld, S. Use of 2 virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms. Vet. Immunol. Immunopathol. 1992, 35, 167-175.
10. (c) Philpott, M. S.; Ebner, J. P.; Hoover, E. A. Evaluation of 9-(2-phosphonylmethoxyethyl)adenine therapy for feline immunodeficiency virus using a quantitative polymerase chain reaction. Vet. Immunol. Immunopathol. 1992, 35, 155-166.
11. (d) Hartmann, K.; Kuffer, M.; Balzarini, J.; Naesens, L.; Goldberg, M.; Erfle, V.; Goebel, F. D.; De Clercq, E.; Jindřich, J.; Holý, A.; Bischofberger, N.; Kraft, W. Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FP-MPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 1998, 17, 120-128.
12. Thormar, H.; Georgsson, G.; Palsson, P. A.; Balzarini, J.; Naesens, L.; Torsteinsdottir, S.; De Clercq, E. Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection in lambs: a model for in vivo testing of candidate anti-human immunodeficiency virus drugs. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 3283-3287.
13. (a) Tsai, C. C.; Follis, K. E.; Sabo, A.; Grant, R. F.; Bartz, C.; Nolte, R. E.; Benveniste, R. E.; Bischofberger, N. Preexposure prophylaxis with 9-(2-phosphonylmethoxyethyl)adenine against simian immunodeficiency virus infection in macaques. J. Infect. Dis. 1994, 269, 260-266.
14. (b) Tsai, C. C.; Follis, K. E.; Sabo, A.; Grant, R.; Bischofberger, N. Efficacy of 9-(2-phosphonylmethoxyethyl)adenine treatment against chronic simian immunodeficiency virus infection in macaques. J. Infect. Dis. 1995, 171, 1338-1343.
15. De Clercq, E.; Holý, A.; Rosenberg, I. Efficacy of phosphonylmethoxyalkyl derivatives of adenine in experimental herpes simplex virus and vaccinia virus infections in vivo. Antimicrob. Agents Chemother. 1989, 33, 185-191.
16. Naesens, L.; Balzarini, J.; De Clercq, E. Therapeutic potential of PMEA as an antiviral drug. Rev. Med. Virol. 1994, 4, 147-159.
17. (a) Starrett, J. E.; Tortolani, D. R.; Hitchcock, M. J. M.; Martin, J. C.; Mansuri, M. M. Synthesis and in vitro evaluation of a phosphonate prodrug - bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine. Antiviral Res. 1992, 19, 267-273.
18. (b) Cundy, K. C.; Fishback, J. A.; Shaw, J. P.; Lee, M. L.; Soike, K. F.; Visor, G. C.; Lee, W. A. Oral bioavailability of the antiretroviral agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) from three formulations of the prodrug bis(pivaloyloxymethyl)-PMEA in fasted male cynomolgus monkeys. Pharmaceut. Res. 1994, 11, 839-843.
19. (c) Naesens, L.; Neyts, J.; Balzarini, J.; Bischofberger, N.; De Clercq, E. In vivo antiretroviral efficacy of oral bis(POM)-PMEA, the bis(pivaloyloxymethyl) prodrug of 9-(2-phosphonylmethoxyethyl)adenine (PMEA). Nucleos. Nucleot. 1995, 14, 767-770.
20. (d) Naesens, L.; Balzarini, J.; Bischofberger, N.; De Clercq, E. Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine. Antimicrob. Agents Chemother. 1996, 40, 22-28.
21. (e) Shaw, J. P.; Louie, M. S.; Krishnamurthy, V. V.; Arimilli, M. N.; Jones, R. J.; Bidgood, A. M.; Lee, W. A.; Cundy, K. C. Pharmacokinetics and metabolism of selected prodrugs of PMEA in rats. Drug Metab. Dispos. 1997, 25, 362-366.
22. (f) Cundy, K. C.; Sue, I. L.; Visor, G. C.; Marshburn, J.; Nakamura, C.; Lee, W. A.; Shaw, J. P. Oral formulations of adefovir dipivoxil: in vitro dissolution and in vivo bioavailability in dogs. J. Pharm. Sci. 1697, 86, 1334-1338.
23. (g) De Clercq, E. New perspectives for the treatment of HIV infections. Collect. Czech. Chem. Commun. 1998, 63, 449-479.
24. Cundy, K. C.; Barditch-Crovo, P. A.; Walker, R. E.; Collier, A. C.; Ebeling, D.; Toole, J.; Jaffe, H. S. Clinical pharmacokinetics of adefovir in human immunodeficiency virus type 1-infected patients. Antimicrob. Agents Chemother. 1895, 39, 2401-2405.
25. (a) Heijtink, R. A.; Dewilde, G. A.; Kruining, J.; Berk, L.; Balzarini, J.; De Clercq, E.; Holý, A.; Schalm, S. W. Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) on human and duck hepatitis-B virus infection. Antiviral Res. 1993, 21, 141-153.
26. (b) Yokota, T.; Konno, K.; Shigeta, S.; Holý, A.; Balzarini, J.; De Clercq, E. Inhibitory effects of acyclic nucleoside phosphonate analogues on hepatitis B virus DNA synthesis in Hb611 Cells. Antivir. Chem. Chemother. 1994, 5, 57-63.
27. (c) Balzarini, J.; Kruining, J.; Heijtink, E.; De Clercq, E. Comparative anti-retrovirus and anti-hepadnavirus activity of three different classes of nucleoside phosphonate derivatives. Antivir. Chem. Chemother. 1994, 5, 360-365.
28. (a) Holý, A.; Votruba, I.; Merta, A.; Černý, J.; Veselý, J.; Vlach, J.; Šedivá, K.; Rosenberg, I.; Otmar, M.; Hřebabecký, H.; Trávníček, M.; Vonka, V.; Snoeck, R.; De Clercq, E. Acyclic nucleotide analogues: synthesis, antiviral activity and inhibition effects on some cellular and virus-encoded enzymes in vitro. Antiviral Res. 1990, 13, 295-312.
29. (b) Merta, A.; Votruba, I.; Rosenberg, I.; Otmar, M.; Hřebabecký, H.; Bernaerts, R.; Holý, A. Inhibition of herpes simplex virus DNA polymerase by diphosphates of acyclic phosphonylmethoxyalkyl nucleotide analogues. Antiviral Res. 1990, 13, 209-218.
30. (c) Foster, S. A.; Černý, J.; Cheng, Y. C. Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine. J. Biol. Chem. 1991, 266, 238-244.
31. (d) Robbins, B. L.; Greenhaw, J.; Connelly, M. C.; Fridland, A. Metabolic pathways for activation of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine in human lymphoid cells. Antimicrob. Agents Chemother. 1995, 39, 2304-2308.
32. Merta, A.; Veselý, J.; Votruba, I.; Rosenberg, I.; Holý, A. Phosphorylation of acyclic nucleotide analogues HPMPA and PMEA in L-1210 mouse leukemic cell extracts. Neoplasma 1990, 37, 111-120.
33. Balzarini, J.; De Clercq, E. 5-Phosphoribosyl 1-pyrophosphate synthetase converts the acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxyethyl)adenine directly to their antivirally active diphosphate derivatives. J. Biol. Chem. 1991, 266, 8686-8689.
34. Kramata, P.; Votruba, I.; Otová, B.; Holý, A. Different inhibitory potencies of acyclic phosphonomethoxyalkyl nucleotide analogues toward DNA polymerases a, δ and ∈. Mol. Pharmacol. 1996, 49, 1005-1011.
35. (a) Votruba, I.; Trávníček, M.; Rosenberg, I.; Otmar, M.; Merta, A.; Hřebabecký, H.; Holý, A. Inhibition of AMV(MAV) reverse transcriptase by diphosphates of acyclic nucleotide analogues. Antiviral Res. 1990, 13, 287-294.
36. (b) Balzarini, J.; Hao, Z.; Herdewijn, P.; Johns, D. G.; De Clercq, E. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 1499-1503.
37. (a) Veselý, J.; Merta, A.; Votruba, I.; Rosenberg, I.; Holý, A. The cytostatic effects and mechanism of action of antiviral acyclic adenine nucleotide analogues in L1210 mouse leukemia cells. Neoplasma 1990, 37, 105-110.
38. (b) Otová, B.; Sladká, M.; Votruba, I.; Holý, A.; Křen, V. Cytostatic effect of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). 1. Lymphatic leukemia KHP-Lw-I in Lewis rats. Folia Biol. Prague 1993, 39, 136-141.
39. (c) Otová, B.; Sladká, M.; Blažek, K.; Schramlová, J.; Votruba, I.; Holý, A. Cytostatic Effect of 9-[2-(phosphonomethoxy)ethyl]-adenine (PMEA). 2. Lymphoblastic leukemia in Sprague-Dawley rats. Folia Biol. Prague 1993, 39, 142.
40. (d) Otová, B.; Křenové, D.; Zídek, Z.; Holý, A.; Votruba, I.; Křen, V. Cytostatic Effect of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). 3. Rat and Mouse Carcinomas and Sarcomas. Folia Biol. Prague 1993, 39, 311-314.
41. (e) Hatse, S.; Naesens, L.; Degreve, B.; Segers, C.; Vandeputte, M.; Waer, M.; De Clercq, E.; Balzarini, J. Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats. Int. J. Cancer 1998, 76, 595-600.
42. (a) Del Gobbo, V.; Foli, A.; Balzarini, J.; De Clercq, E.; Balestra, E.; Villani, N.; Marini, S.; Perno, C. F.; Calio, R. Immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent anti-HIV nucleotide analogue, on in vivo in urine models. Antiviral Res. 1991, 16, 65-75.
43. (b) Křen, V.; Otová, B.; Elleder, D.; Elleder, M.; Panczak, A.; Holý, A. Prevention of acute graft-versus-host disease in rats using 9-[2-(phosphonomethoxy)ethyl]-adenine (PMEA). Folia Biol. Prague 1993, 39, 78-86.
44. (c) Otová, B.; Zídek, Z.; Holý, A.; Votruba, I.; Franková, D. Immunomodulatory properties of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). Folia Biol. Prague 1994, 40, 185-192.
45. (d) Villani, N.; Calio, R.; Balestra, E.; Balzarini, J.; De Clercq, E.; Fabrizi, E.; Perno, C. F.; Del Gobbo, V. 9-(2-phosphonylmethoxyethyl)-adenine increases the survival of influenza virus-infected mice by an enhancement of the immune system. Antiviral Res. 1994, 25, 81-89.
46. (e) Calio, R.; Villani, N.; Balestra, E.; Sesa, F.; Holý, A.; Balzarini, J.; De Clercq, E.; Perno, C. F.; Del Gobbo, V. Enhancement of natural killer activity and interferon induction by different acyclic nucleoside phosphonates. Antiviral Res. 1994, 23, 77-89.
47. (f) Zídek, Z.; Holý, A.; Franková, D.; Otová, B. Suppression of rat adjuvant arthritis by some acyclic nucleotide analogues. Eur. J. Pharmacol. 1993, 286, 307-310.
48. (g) Zídek, Z.; Franková, D.; Holý, A.; Boubelík, M.; Dráber, P. Inhibition of murine macrophage nitric oxide synthase expression by a pivoxil prodrug of antiviral acyclic nucleotide analogue 9-(2-phosphonomethoxyethyl)adenine. Biochem. Pharmacol. 1997, 54, 855-861.
49. (h) Balzarini, J.; Verstuyf, A.; Hatse, S.; Goebels, J.; Sobis, H.; Vandeputte, M.; De Clercq, E. The human immunodeficiency virus (HIV) inhibitor 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a strong inducer of differentiation of several tumor cell lines. Int. J. Cancer 1995, 61, 130-137.
50. (i) Hatse, S.; De Clercq, E.; Balzarini, J. The role of antimetabolites of purine and pyrimidine metabolism in tumor cell differentiation. Biochem. Pharmacol. 1998, in press.
51. (a) Baba, M.; Konno, K.; Shigeta, S.; De Clercq, E. In vitro activity of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine against newly isolated clinical varicella-zoster virus strains. Eur. J. Clin. Microbiol. Infect. Dis. 1987, 6, 158-160.
52. (b) Maudgal, P. C.; De Clercq, E.; Huyghe, P. Efficacy of (S)-HPMPA against thymidine kinase deficient herpes simplex virus keratitis. Invest. Ophthalmol. Vis. Sci. 1987, 28, 243-248.
53. (c) Mul, Y. M.; van Miltenburg, R. T.; De Clercq, E.; Van der Vliet, P. C. Mechanism of inhibition of adenovirus DNA replication by the acyclic nucleoside triphosphate analogue (S)-HPMPApp; influence of the adenovirus DNA binding protein. Nucl. Acids Res. 1989, 17, 8917-8929.
54. (a) Terry, B. J.; Mazina, K. E.; Tuomari, A. V.; Haffey, M. L.; Hagen, M.; Feldman, A.; Slusarchyk, W. A.; Young, M. G.; Zahler, R.; Field, A. K. Broad-spectrum antiviral activity of the acyclic guanosine phosphonate (R,S)-HPMPG. Antiviral Res. 1988, 10, 235-251.
55. (b) Yu, KL.; Bronson, J. J.; Yang, H.; Patick, A.; Alam, M.; Brankovan, V.; Datema, R.; Hitchcock, M. J.; Martin, J. C. Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine. J. Med. Chem. 1992, 35, 2958-2969.
56. (c) Smee, D. F.; Barnett, B. B.; Sidwell, R. W.; Reist, E. J.; Holý, A. Antiviral activities of nucleosides and nucleotides against wild-type and drug-resistant strains of murine cytomegalovirus. Antiviral Res. 1905, 26, 1-9.
57. (a) Neyts, J.; Snoeck, R.; Balzarini, J.; De Clercq, E. Particular characteristics of the anti-human cytomegalovirus activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in vitro. Antiviral Res. 1991, 16, 41-52.
58. (b) De Clercq, E. Therapeutic potential of HPMPC as an antiviral drug. Rev. Med. Virol. 1993, 3, 85-96.
59. (c) Holý, A. Syntheses of enantiomeric N-(3-hydroxy-2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases. Collect. Czech. Chem. Commun. 1993, 58, 649-674.
60. (d) Flores-Aguilar, M.; Huang, J.-S.; Wiley: C. A.; De Clercq, E.; Vuong, C.; Bergeron-Lynn, G. L.; Chandler, B.; Munguia, D.; Freeman, W. R. Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. J. Infect. Dis. 1994, 169, 642-647.
61. (e) Kirsch, L. S.; Arevalo, J. F.; Delapaz, E. C.; Munguia, D.; De Clercq, E.; Freeman, W. R. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology 1996, 102, 533-542.
62. (f) Blick, G.; Garton, T.; Hopkins, U.; Lagravinese, L. Successful use of cidofovir in treating AIDS-related cytomegalovirus retinitis, encephalitis, and esophagitis. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 1997, 15, 84-85.
63. (g) Naesens, L.; De Clercq, E. Therapeutic potential of HPMPC (cidofovir), PMEA (adefovir) and related acyclic nucleoside phosphonate analogues as broad-spectrum antiviral agents. Nucleos. Nucleot. 1997, 16, 983-992.
64. (h) Lalezari, J. P.; Holland, G. N.; Kramer, F.; McKinley, G. F.; Kemper, C. A.; Ives, D. V.; Nelson, R.; Hardy, W. D.; Kuppermann, B. D.; Northfelt, D. W.; Youle, M.; Johnson, M.; Lewis, R. A.; Weinberg, D. V.; Simon, G. L.; Wolitz, R. A.; Ruby, A. E.; Stagg, R. J.; Jaffe, H. S. Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 1998, 17, 339-344.
65. (a) Hitchcock, M. J. M.; Jaffe, H. S.; Martin, J. C.; Stagg, R. J. Cidofovir, a new agent with potent anti-herpesvirus activity -Review: Antiviral portrait series. Antivir. Chem, Chemother. 1996, 7, 115-127.
66. (b) Lea, A. P.; Bryson, H. M. Cidofovir. Drugs 1996, 52, 225-230.
67. (c) Rahhal, F. M.; Arevalo, J. F.; Munguia, D.; Taskintuna, I.; Delapaz, E. C.; Azen, S. P.; Freeman, W. R. Intravitreal cidofovir for the maintenance treatment of cytomegalovirus retinitis. Ophthalmology 1998, 103, 1078-1083.
68. (d) De Clercq, E. Towards an effective chemotherapy of virus infections: Therapeutic potential of cidofovir [(S)-1-[3-hydroxy2-(phosphonomethoxy)propyl]cytosine, HPMPC] for the treatment of DNA virus infections. Collect. Czech. Chem. Commun. 1998, 63, 480-606.
69. (a) Snoeck, R.; Van Ranst, M.; Andrei, G.; De Clercq, E.; Dewit, S.; Poncin, M.; Clumeck, N. Treatment of anogenital papillomavirus infections with an acyclic nucleoside phosphonate analogue. N. Engl. J. Med. 1995, 333, 943-944.
70. (b) Van Cutsem, E.; Snoeck, R.; Van Ranst, M.; Fiten, P.; Opdenakker, G.; Geboes, K.; Janssens, J.; Rutgeerts, P.; Van Trappen, G.; De Clercq, E. Successful treatment of a squamous papilloma of the hypopharynx - esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. J. Med. Virol. 1995, 45, 230-235.
71. (c) Meadows, K. P.; Tyring, S. K.; Pavia, A. T.; Rallis, T. M. Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir. Arch. Dermatol. 1997, 133, 987-990.
72. (d) Zabawski, E. J., Jr.; Sands, B.; Goetz, D.; Naylor, M.; Cockerell, C. J. Treatment of verruca vulgaris with topical cidofovir. JAMA 1997, 278, 1236.
73. (e) Blick, G.; Whiteside, M.; Griegor, P.; Hopkins, U.; Garton, T.; Lagravinese, L. Successful resolution of progressive multifocal leukoencephalopathy after combination therapy with cidofovir and cytosine arabinoside. Clin. Infect. Dis. 1998, 26, 191-192.
74. (f) Snoeck, R.; Wellens, W.; Desloovere, C.; Van Ranst, M.; Naesens, L.; De Clercq, E.; Feenstra, L. Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine]. J. Med. Virol. 1998, 54, 219-225.
75. (g) Neyts, J.; Sadler, R.; De Clercq, E.; Raab-Traub, N.; Pagano, J. S. The antiviral agent cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice. Cancer Res. 1998, 58, 384-388.
76. (a) Balzarini, J.; Holý, A.; Jindřich, J.; Dvořáková, H.; Hao, Z.; Snoeck, R.; Herdewijn, P.; Johns, D. G.; De Clercq, E. 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 4961-4965.
77. b) Jindřich, J.; Holý, A.; Dvořáková, H. Synthesis of N-(3-fluoro-2-phosphonomethoxypropyl) (FPMP) derivatives of heterocyclic bases. Collect. Czech. Chem. Commun. 1993, 58, 1645-1667.
78. Balzarini, J.; Holý, A.; Jindřich, 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 anti-retrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob. Agents Chemother. 1993, 37, 332-338.
79. (b) Holý, A., Masojídková, M. Synthesis of enantiomeric N-(2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases. 1. The stepwise approach. Collect. Czech. Chem. Commun. 1995, 60, 1196-1212.
80. (c) Holý, A.; Dvořáková, H.; Masojídková, M. Synthesis of enantiomeric N-(2-phosphonomethoxypropyl) derivatives of heterocyclic bases. 2. Synthon approach. Collect. Czech. Chem. Commun. 1995, 60, 1390-1409.
81. (d) Balzarini, J.; Aquaro, S.; Perno, C. F.; Witvrouw, M.; Holý, A.; De Clercq, E. Activity of the (R)-enantiomers of 9-(2-phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems. Biochem. Biophys. Res. Commun. 1996, 219, 337-341.
82. 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, 1197-1199.
83. (b) 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, 1197-1199.
84. (a) Dvořáková, H.; Holý, A.; Rosenberg, I. Synthesis of some 2′-C-alkyl derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine and related compounds. Collect. Czech. Chem. Commun. 1994, 59, 2069-2094.
85. (b) Liboska, R.; Masojídková, M.; Rosenberg, I. Carbocyclic phosphonate-based nucleotide analogues related to PMEA. 1. Racemic trans-configured derivatives. Collect. Czech. Chem. Commun. 1996, 61, 313-332.
86. (c) Alexander, P.; Krishnamurthy, V. V.; Prisbe, E. J. Synthesis and antiviral activity of pyranosylphosphonic acid nucleotide analogues. J. Med. Chem. 1996,39, 1321-1330.
87. (a) Holý, A.; De Clercq, E.; Votruba, I.: Phosphonylmethyl ethers of nucleosides and their acyclic analogues. In Nucleotide Analogues as Antiviral Agents; Martin, J. C., Ed.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989; pp 51-71.
88. (b) Bronson, J. J.; Kim, C. U.; Ghazzouli, I.; Hitchcock, M. J. M.; Kern, E. R.; Martin, J. C. Synthesis and antiviral activity of phosphonylmethoxyethyl derivatives of purine and pyrimidine bases. In Nucleotide Analogues as Antiviral Agents; Martin, J. C., Ed.; American Chemical Society: Washington, 1989; pp 72-87.
89. (c) Holý, A.: Isopolar Phosphorus-Modified Nucleotide Analogues. In Advances in Antiviral Drug Design; De Clercq, E., Ed.; JAI Press: Greenwich, CT, 1994; pp 179-232.
90. (a) Naesens, L.; Balzarini, J.; Rosenberg, I.; Holý, A.; De Clercq, E. 9-(2-Phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP): A novel agent with anti-human immunodeficiency virus activity in vitro and potent anti-Moloney murine sarcoma virus activity in vivo. Eur. J. Clin. Microbiol. Infect. Dis. 1989, 8, 1043-1047.
91. (b) Naesens, L.; Balzarini, J.; De Clercq, E. Single-dose administration of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) in the prophylaxis of retrovirus infection in vivo. Antiviral Res. 1991, 16, 53-64.
92. (c) Naesens, L.; Neyts, J.; Balzarini, J.; Holý, A.; Rosenberg, I.; De Clercq, E. Efficacy of oral 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) in the treatment of retrovirus and cytomegalovirus infections in mice. J. Med. Virol. 1993, 39, 167-172.
93. (a) Kreider, J. W.; Balogh, K.; Olson, R. O.; Martin, J. C. Treatment of latent rabbit and human papillomavirus infections with 9-(2-phosphonylmethoxy)ethylguanine (PMEG). Antiviral Res. 1990, 14, 51-58.
94. (b) Ho, H. T.; Woods, K. L.; Konrad, S. A.; De Boeck, H.; Hitchcock, M. J. Cellular metabolism and enzymatic phosphorylation of 9-(2-phosphonylmethoxyethyl) guanine (PMEG), a potent antiviral agent. Adv. Exp. Med. Biol. 1992, 312, 159-166.
95. Rose, W. C.; Crosswell, A. R.; Bronson, J. J.; Martin, J. C. In vivo antitumor activity of 9-[(2-phosphonylmethoxy)ethyl]guanine and related phosphonate nucleotide analogues. J. Natl. Cancer Inst. 1990, 82, 510-512.
96. Krejčová, R.; Horská, K.; Votruba, I.; Holý, A. Phosphorylation of phosphonomethoxyalkylguanines by GMP-kinase isoenzymes. Collect. Czech. Chem. Commun. 1996, 61, S134-S136.
97. Šedivá, K.; Ananiev, A. V.; Votruba, I.; Holý, A.; Rosenberg, I. Inhibition of purine nucleoside phosphorylase by phosphonylmethyl analogues of nucleotides. Int. J. Purine Pyrim. Res. 1991, 2, 35-40.
98. (a) Dvořáková, H.; Holý, A.; Masojídková, M.; Votruba, I.; Balzarini, J.; Snoeck, R.; De Clercq, E. Synthesis and antiviral activity of acyclic nucleoside and nucleotide derivatives of 8-azaadenine. Collect. Czech. Chem. Commun. Special Issue No. 1. 1993, 58, 253-255.
99. (b) Holý, A.; Dvořáková, H.; Jindřich, J.; Masojídková, M.; Buděšínský, M.; Balzarini, J.; Andrei, G.; De Clercq, E. Acyclic nucleotide analogues derived from 8-azapurines: Synthesis and antiviral activity. J. Med. Chem. 1996, 39, 4073-4088.
100. (a) Dvořáková, H.; Holý, A.; Snoeck, R.; Balzarini, J.; De Clercq, E. Acyclic Nucleoside and Nucleotide Analogues Derived from 1-Deaza and 3-Deazaadenine. Collect. Czech. Chem. Commun. Special Issue No. 1. 1990, 55, 113-116.
101. (b) Dvǒáková, H.; Holý, A. Synthesis and biological effects of N-[2-(phosphonomethoxy)-ethyl] derivatives of deazapurine bases. Collect. Czech. Chem. Commun. 1993, 55, 1419-1429.
102. Holý, A.; Rosenberg, I.; Dvořáková, H. Synthesis of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases. Collect. Czech. Chem. Commun. 1989, 54, 2190-2210.
103. (a) Holý, A.; Rosenberg, I. Synthesis of 9-(2-phosphonylmethoxyethyl)adenine and related compounds. Collect. Czech. Chem. Commun. 1987, 52, 2801-2809.
104. (b) Rosenberg, I.; Holý, A.; Masojídková, M. Phosphonylmethoxyalkyl and phosphonylalkyl derivatives of adenine, Collect. Czech. Chem. Commun. 1988, 53, 2753-2777.
105. Glycosylation of scarcely soluble pteridine derivative with halogenose in the presence of DBU was recently described: Jungmann, O.; Pfleiderer, W. New efficient method in nucleoside synthesis. Tetrahedron Lett. 1996, 37, 8355-8358.
106. Holý, A.; Zídek, Z.; Votruba, I. Inhibition of murine lymphocyte proliferation by N-6-substituted acyclic purine nucleoside phosphonates. Collect. Czech. Chem. Commun. 1998, 61, S182-S187.
107. Linn, J. A.; McLean, E.; Kelley, J. L. 1,4-Diazabicyclo[2,2,2]-octane (DABCO)-catalyzed hydrolysis and alcoholysis reactions of 2-amino-9-benzyl-6-chloro-9H-purine. J. Chem. Soc., Perkin Trans, 1. 1994, 1994, 913-914.
108. Okumura, K.; Oine, T.; Yamada, Y.; Tomie, M.; Adachi, T.; Nagura, T.; Kawazu, M.; Mizoguchi, T.; Inoue, I. Synthetic Studies on eritadenine I. Reactions of some purines with the 2,3-O-protected dihydroxybutyrolactone. J. Org. Chem. 1973, 36, 1573-1579.
109. Mangalagiu, I.; Benneche, T.; Undheim, K. Trialkylalanes in palladium-catalyzed chemo-and regioselective alkylations. Tetrahedron Lett. 1996, 37, 1309-1312.
110. For review: Revankar, G. R.; Robins, R. K.; Heterocyclic Analogues of Purine Nucleosides and Nucleotides. In Chemistry of Nucleosides and Nucleotides; (Townsend, L. B., Ed.); Plenum Press: New York, 1988; Vol. 2, pp 200-246.
111. Eistetter, K.; Pfleiderer, W. Nucleosid-Synthesen in der Pterin-Reihe. Chem. Ber. 1976, 109, 3208-3216.
112. Holý, A. Simple method for cleavage of phosphonic acid diesters to monoesters. Synthesis 1998, 381-385.
113. Fujii, Y.; Mukai, R.; Mori, K.; Akari, H.; Otani, I.; Ono, F.; Kojima, E.; Takasaka, M.; Machida, M.; Murakami, K.; Yoshikawa, Y. Efficacy of 6-chloro-2′,3′-dideoxyguanosine (6-Cl-ddG) on rhesus macaque monkeys chronically infected with simian immunodeficiency virus (SIVmac239). J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 1997, 16, 313-317.
114. Alexander, P.; Holy′, A. Prodrugs of Analogues of Nucleic Acid Components. Collect. Czech. Chem. Commun. 1994, 59, 2127-2165.
115. Arnold, Z.; Kornilov, M. Reactivity of 1,1-dialkoxytrimethylamines. Collect. Czech. Chem. Commun. 1965, 29, 645-651.
116. Votruba, I.; Holý, A.; Dvořáková, H.; Günter, J.; Hocková, D.; Hřebabecký, H.; Cihlář, T.; Masojídková, M. Synthesis of 2-deoxy-β-D-ribonucleosides and 2,3-dideoxy-β-D-pentafuranosides on immobilized bacterial cells. Collect. Czech. Chem. Commun. 1994, 59, 2303-2330.
117. Fisher, E. C.; Joullié, M. M. Preparation of 5(6)-fluorobenzimidazole and 4(7)-fluorobenzimidazole. J. Org. Chem. 1958, 83, 1944-1946.
118. Francis, J. H.; Moskal, M. A. A general synthesis of 5,7-diaminoimidazo[4,5-b]pyridine ribosides ("2-amino-1-deazaadenosines") from 5-amino-4-imidazolecarboxamide riboside (AICA riboside). Can. J. Chem. 1992, 70, 1288-1295.
119. Rousseau, R. J.; May, jr. J. A.; Robins, R. K.; Townsend, L. B. The synthesis of 3-deaza-6-thioguanine and certain related derivatives. J. Heterocyclic Chem. 1974, 11, 233-235.
120. Enoki, K.; Hinoki, Y.; Genda, Y. Japan Kokai 7676,290; Chem. Abstr. 1992, 86, P43727k.
121. Brown, D. J.; Jacobsen N. W. Pteridine studies. Part XIV. Methylation of 2-amino-4-hydroxypteridine and related compounds. J. Chem. Soc. 1961, 4413-4420.
122. De Clercq, E.; Descamps, J.; Verhelst, G.; Walker, R. T.; Jones, A. S.; Torrence, P. F.; Shugar, D. Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J. Infect. Dis. 1980, 141, 563-574.