Synthesis of novel difluoro-cyclopropyl guanine nucleosides and their phosphonate analogues as potent antiviral agents

Nucleosides, Nucleotides and Nucleic Acids

Volumn 30, Issue 11, 2011, Pages 945-960

  Li, Hua ^a   Yoo, Jin Cheol ^a   Kim, Eunae ^a   Hong, Joon Hee ^a  

^a Chosun University   (South Korea)

Author keywords

Antiviral agents; Difluorination; Nucleoside analogues

Indexed keywords

9 [1,2 BIS(HYDROXYMETHYL)CYCLOPROPYLMETHYL]GUANINE; ACICLOVIR; ADEFOVIR; NUCLEOSIDE ANALOG; PHOSPHONIC ACID DERIVATIVE; SYNGUANOL; TENOFOVIR; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOMEGALOVIRUS; DRUG SYNTHESIS; HERPES VIRUS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY;

ANTIVIRAL AGENTS; CELL LINE; CYCLOPROPANES; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; GUANINE; HALOGENATION; HIV INFECTIONS; HIV-1; HUMANS; NUCLEOSIDES; PHOSPHONIC ACIDS;

HERPES; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84862956946     PISSN: 15257770     EISSN: 15322335     Source Type: Journal    
DOI: 10.1080/15257770.2011.625374     Document Type: Article

References (25)

1. 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. (Pubitemid 8305178)
2. a) 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;
3. Snoeck, R.; Sakuma, T.; De Clercq, E.; Rosenberg, I.; Holy, A. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine, apotent and selective inhibitor of human cytomegalovirus replication. Antimicrob. Agents Chemother. 1988, 32, 1839-1844.
4. a) Votruba, I.; Bernaerts, R.; Sakuma, T.; De Clercq, E.; Merta, A.; Rosenberg, I.; Holý, A. Intracellular phosphorylation of broad-spectrum anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine and inhibition of viral DNA synthesis. Mol. Pharmacol. 1987, 32, 524-529; (Pubitemid 18006154)
5. Balzarini, J.; Hao, Z.; Herdewijn, P.; Johns, D. G.; De Clercq, E. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonyl methoxyethyl) adenine, a potent antihuman immunodeficiency virus compound. Proc. Natl. Acad. Sci. USA 1991, 88, 1499-1503. (Pubitemid 21916252)
6. Kim, C. U.; Luh, B. Y.; Martin, J. C. Regiospecific and highly stereoselective electrophilic addition to furanoid glycals: Synthesis of phosphonate nucleotide analogs with potent activity against HIV. J. Org. Chem. 1991, 56, 2642-2647.
7. a) For a review, see: Naesens, l.; Balzarini, J.; De Clercq, E. Therapeutic potential of PMEA as an antiviral drug. Med. Virol. 1994, 4, 147-159;
8. De Clercq, E. Broad-spectrum anti-DNA virus and anti-retrovirus activity of phosphonylmethoxyalkylpurines and-pyrimidines. Biochem. Pharmacol. 1991, 42, 963-972;
9. Balzarini, J.; Naesens, L.; Slachmuylders, J.; Niphuis, H.; Rosenberg, I.; Holý, A.; Schellekens, H.; De Clercq, E. 9-(2-Phosphonylmethoxyethyl) adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys. AIDS 1991, 5, 21-28.
10. Robbins, B. L.; Srinivas, R. V.; Bischofberger, N.; Fridland, A. Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2- phosphonomethoxypropyl) adenine (PMPA), Bis (isopropyloxymethylcarbonyl) PMPA. Antimicrob. Agents Chemother. 1998, 42, 612-617. (Pubitemid 28114817)
11. a) Kwak, E.; Hong, J. H.; Park, J.; Choi, B. G. Synthesis and antiviral activity of novel C-methyl branched cyclopropyl nucleosides. Arch. Pharm. Res. 2003, 26, 679-685;
12. Kim, J. W.; Ko, O. H.; Hong, J. H. Synthesis and antiviral evaluation ofnovel methyl branched cyclopropyl phosphonic acid nucleosides. Arch. Pharm. Res. 2005, 28, 745-749;
13. Kim, A.; Hong, J. H.; Oh, C. H. Synthesis and anti-HCMV activity of novel cyclopropyl phosphonic acid nucleosides. Arch. Pharm. Res. 2006, 339, 507-512.
14. Sekiyama, T.; Hatsuya, S.; Tanaka, Y.; Uchiyama, M.; Ono, N.; Iwayama, S.; Oikawa, M.; Suzuki, K., Okunishi, M.; Tsuji, T. Synthesis and antiviral activity of novel acyclic nucleosides: Discovery of a cyclopropyl nucleoside with potent inhibitory activity against herpesviruses. J. Med. Chem. 1998, 41, 1248-1298.
15. Harnden, M. R.; Jarvest, R. L.; Bacon, T. H.; Boyd, M. R. Synthesis and antiviral activity of 9-[4-hydroxy-3-(hydroxymethyl) but-1-yl]purines. J. Med. Chem. 1987, 30, 1636-1642. (Pubitemid 17135911)
16. Qui, Y. L.; Ksebati, M. B.; Zemlicka, J. Synthesis of (Z) - and (E)-9-[(2-hydroxyethylidene) cyclopropyl]adenine-new methylenecyclopropane analogues of adenosine and their substrate activity for adenosine deaminase. Nucleosides, Nucleotides Nucleic Acids 2000, 19, 31-37. (Pubitemid 30230028)
17. Hong, J. H.; Ko, O. H. Synthesis and antiviral evaluation of novel acyclic nucleosides. Bull. Korean Chem. Soc. 2003, 24, 1284-1288.
18. a) Csuk, R.; Thiede, G. Preparation of novel difluorocyclopropane nucleosides. Tetrahedron. 1999, 55, 739-750; (Pubitemid 29023319)
19. Csuk, R.; Eversmann, L. Synthesis of difluorocyclopropyl carbocyclic homo-nucleosides. Tetrahedron 1998, 54, 6445-6456. (Pubitemid 28231255)
20. Borcherding, D. R.; Narayanan, S.; Hasobe, M.; McKee, J. G.; Keller, B. T.; Borchardt, R. T. Potential inhibitors of S-adenosylmethionine-dependent methyltransferases: Molecular dissections of neplanocin A as potential inhibitors of S-adenosylhomocysteine hydrolase. J. Med. Chem. 1988, 31, 1729-1738.
21. a) Phillion, D. P.; Andrew, S. S. Synthesis and reactivity of diethyl phosphonomethyltriflate. Tetrahedron Lett. 1986, 27, 1477-1480;
22. Xu, Y.; Flavin, M. T.; Xu, Z.-Q. Preparation of new Wittig reagents and their application to the synthesis of α, β-unsaturated phosphonates. J. Org. Chem. 1996, 61, 7697-7701. (Pubitemid 126526018)
23. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J. Virol. Methods 1988, 20, 309-321.
24. Yu, K. L.; 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.
25. Tsai, C. C.; Follis, K. E.; Grant, R.; Sabo, A.; Nolte, R.; Bartz, C.; Bischofberger, N.; Benveniste, R. Comparison of the efficacy of AZT and PMEA treatment against acute SIV infection in macaques. J. Med. Primatol. 1994, 23, 175-183.