Synthesis and biological activity of 2-aminopurine methylenecyclopropane analogues of nucleosides

Nucleosides, Nucleotides and Nucleic Acids

Volumn 22, Issue 2, 2003, Pages 135-144

  Wang, Ruifang ^a   Chen, Xinchao ^a   Drach, John C ^b   Kern, Earl R ^c   Zemlicka, Jiri ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c University of Alabama at Birmingham   (United States)

Author keywords

2 aminopurine; Alkylation elimination; Methylenecyclopropanes; Nucleoside analogues; Prodrugs; Xanthine oxidase

Indexed keywords

2 AMINO 7 [(2 HYDROXYMETHYL)CYCLOPROPYLIDENEMETHYL]PURINE; 2 AMINO 9 [(2 HYDROXYMETHYL)CYCLOPROPYLIDENEMETHYL]PURINE; 2 AMINOPURINE; 2 AMINOPURINE METHYLENECYCLOPROPANE; 6 THIOSYNGUANOL; BROMINE DERIVATIVE; DIBROMIDE; NICKEL; NUCLEOSIDE DERIVATIVE; SILICA GEL; UNCLASSIFIED DRUG;

ALKYLATION; ANTIVIRAL ACTIVITY; ARTICLE; CELL STRAIN KB; CHEMICAL MODIFICATION; CHEMICAL REACTION; CHROMATOGRAPHY; CONTROLLED STUDY; DEACETYLATION; DESULFURIZATION; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ELIMINATION REACTION; ENANTIOMER; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME SUBSTRATE; EPSTEIN BARR VIRUS; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; ISOMER; NONHUMAN; VARICELLA ZOSTER VIRUS; VIRUS CULTURE; VIRUS REPLICATION;

2-AMINOPURINE; ALKYLATION; ANTIVIRAL AGENTS; CHROMATOGRAPHY, GEL; CYCLOPROPANES; MODELS, CHEMICAL; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; NUCLEOSIDES; PRODRUGS; SPECTROPHOTOMETRY, ULTRAVIOLET; STEREOISOMERISM; XANTHINE OXIDASE;

HERPES; HUMAN HERPESVIRUS 1; HUMAN HERPESVIRUS 2; HUMAN HERPESVIRUS 3; HUMAN HERPESVIRUS 4; HUMAN HERPESVIRUS 5;

EID: 0037264387     PISSN: 15257770     EISSN: None     Source Type: Journal    
DOI: 10.1081/NCN-120019502     Document Type: Article

References (16)

1. Qiu, Y.-L.; Ksebati, M.B.; Ptak, R.G.; Boreas, Y.F.; Breitenbach, J.M.; Lin, J.-S.; Cheng, Y.-C.; Kern, E.R.; Drach, J.C.; Zemlicka, J. (Z) and (E)-2-((Hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity. J. Med. Chem. 1998, 41, 10-23.
2. Qiu, Y.-L.; Ptak, R.G.; Breitenbach, J.M.; Lin, J.-S.; Cheng, Y.-C.; Drach, J.C.; Kern, E.R.; Zemlicka, J. (Z)- and (E)-2-(hydroxymethylcyclopropylidene)methylpurines and pyrimidines as antiviral agents. Antiviral Chem. Chemother 1998, 9, 341-352.
3. Qiu, Y.-L.; Geiser, F.; Kira, T.; Gullen, E.; Cheng, Y.-C.; Ptak, R.G.; Breitenbach, J.M.; Drach, J.C.; Hartline, C.B.; Kern, E.R.; Zemlicka, J. Synthesis and enantioselectivity of the antiviral effects of (R,Z)-,(S,Z)-methylenecyclopropane analogues of purine nucleosides and phosphoralaninate prodrugs: influence of heterocyclic base, type of virus and host cells. Antiviral Chem. Chemother. 2000, 11, 191-202.
4. Rybak, R.J.; Zemlicka, J.; Qui, Y.-L.; Hartline, C.B.; Kern, E.R. Effective treatment of murine cytomegalovirus infections with methylenecyclopropane analogues of nucleosides. Antiviral Res. 1999, 43, 175-188.
5. Bidanset, D.J.; Hartline, C.B.; Collins, D.J.; Quenelle, D.C.; Chen, X.; Zemlicka, J.; Kern, E.R. In vitro and in vivo activity of the methylenecyclopropane analog, QYL-1064, against murine and human cytomegalovirus infections. Antiviral Res. 2002, 53, A61.
6. Krenitsky, T.A.; Hall, W.W.; de Miranda, P.; Beauchamp, L.M.; Schaeffer, H.J.; Whiteman, P.D. 6-Deoxyacyclovir: A xanthine oxidase-activated prodrug of acyclovir. Proc. Natl. Acad. Sci. USA 1984, 81, 3209-3213.
7. Harnden, M.R.; Jarvest, R.L.; Boyd, M.R.; Sutton, D.; Vere Hodge, R.A. Prodrugs of selective antiherpesvirus agent 9-[4-Hydroxy-3-(hydroxymethyl)but-1-yl]guanine (BRL 39123) with improved gastrointestinal absorption properties. J. Med. Chem. 1989, 32, 1738-1743.
8. Jahne, G.; Kroha, H.; Muller, A.; Helsberg, M.; Winkler, I.; Gross, G.; Scholl, T. Regioselective synthesis and antiviral activity of purine nucleoside analogues with acyclic substituents at N7. Angew. Chem. Int. Ed. Engl. 1994, 33, 562-563.
9. Neyts, J.; Andrei, G.; Snoeck, R.; Jahne, G.; Winkler, I.; Helsberg, M.; Balzarini, J.; De Clercq, E. The N-7-substituted acyclic nucleoside analog 2-Amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine is a potent and selective inhibitor of herpesvirus replication. Antimicrob. Agents Chemother. 1994, 38, 2710-2716.
10. Meerbach, A.; Holy, A.; Wutzler, P.; De Clercq, E.; Neyts, J. Inhibitory effects of novel nucleoside and nucleotide analogues on Epstein-Barr virus replication. Antiviral Chem. Chemother 1998, 9, 275-282.
11. Neyts, J.; Jahne, G.; Andrei, G.; Snoeck, R.; Winkler, I.; De Clercq, E. In Vitro antiherpesvirus activity of N-7-substituted acyclic nucleoside analog 2-Amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine. Antimicrob. Agents Chemother. 1995, 39, 56-60.
12. Garner, P.; Yoo, J.U.; Sarabu, R. Synthesis of 2-aminopurine nucleosides via regiocontrolled glycosylation. Tetrahedron 1992, 48, 4259-4270.
13. Qiu, Y.-L.; Zemlicka, J. A new efficient synthesis of antiviral methylenecyclopropane analogs of purine nucleosides. Synthesis 1998, 1447-1452.
14. Chen, X.; Zemlicka, J. Revision of absolute configuration of enantiomeric (methylenecyclopropyl)carbinols obtained from (R)-(-)- and (S)-(+)-epichlorohydrin and methylenetriphenylphosphorane. Implications for reaction mechanism and improved synthesis of antiviral methylenecyclopropane analogues of nucleosides. J. Org. Chem. 2002, 67, 286-289.
15. Kjellberg, J.; Johansson, N.G. Studies on the alkylation of derivatives of guanine. Nucleosides & Nucleotides 1989, 8, 225-256.
16. 13C NMR. Tetrahedron 1986, 42, 6541-6544.