Synthesis of 5′-triphosphate mimics (P3Ms) of 3′-azido- 3′,5′-dideoxythymidine and 3′,5′-dideoxy-5′- difluoromethylenethymidine as HIV-1 reverse transcriptase inhibitors

Nucleosides, Nucleotides and Nucleic Acids

Volumn 24, Issue 3, 2005, Pages 179-189

  Rajwanshi, Vivek K ^a   Prhavc, Marija ^a   Fagan, Patrick ^a   Brooks, Jennifer L ^a   Hurd, Tiffany ^a   Cook, P Dan ^a   Wang, Guangyi ^a  

^a Biota Inc   (United States)

Author keywords

5 Deoxynucleotides; HIV 1 RT; Synthesis; Triphosphate Mimics

Indexed keywords

3' AZIDO 3',5' DIDEOXYTHYMIDINE; 3' AZIDO 3',5' DIDEOXYTHYMIDINE 5' PHOSPHONATE; 3',5' DIDEOXY 5' DIFLUOROMETHYLENETHYMIDINE; 3',5' DIDEOXY 5' DIFLUOROMETHYLENETHYMIDINE 5' PHOSPHONATE; BETA,GAMMA DICHLOROMETHYLENETHYMIDINE TRIPHOSPHATE; BETA,GAMMA DIFLUOROMETHYLENETHYMIDINE TRIPHOSPHATE; BETA,GAMMA IMIDOTHYMIDINE TRIPHOSPHATE; NUCLEOSIDE 5' PHOSPHONATE; NUCLEOSIDE TRIPHOSPHATASE; PYROPHOSPHATE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMIDINE DERIVATIVE; UNCLASSIFIED DRUG; 3',5'-DIDEOXY-5'-DIFLUOROMETHYLENETHYMIDINE; 3'-AZIDO-3'-DEOXYTHYMIDINE 5'-TRIPHOSPHATE; DRUG DERIVATIVE; PYRIMIDINE NUCLEOTIDE; THYMIDINE; ZIDOVUDINE; ZIDOVUDINE 5' TRIPHOSPHATE;

ARTICLE; ENZYME INHIBITION; ENZYME SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN IMMUNODEFICIENCY VIRUS 1; PHOSPHORUS NUCLEAR MAGNETIC RESONANCE; POLYMERIZATION; PROTON NUCLEAR MAGNETIC RESONANCE; SYNTHESIS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; MOLECULAR MIMICRY; STRUCTURE ACTIVITY RELATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

HIV-1 REVERSE TRANSCRIPTASE; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THYMIDINE; THYMINE NUCLEOTIDES; ZIDOVUDINE;

EID: 18044392735     PISSN: 15257770     EISSN: None     Source Type: Journal    
DOI: 10.1081/NCN-200055707     Document Type: Article

References (15)

1. Herdewijn, P.; Balzarini, J.; De Clercq, E. 2′-3′- Dideoxynucleoside analogues as antiviral agents. In Advances in Antiviral Drug Design; De Clercq, E., Ed.; JAI Press, Inc.: Greenwich, 1993; Vol. 1.
2. St. Claire, M.H.; Richards, C.A.; Spector, T.; Weinhold, K.J.; Langlois, Miller A.J.; Furman, P.A. 3′-Azido-3′-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase. Antimicrob. Agents Chemother. 1987, 31, 1972-1977.
3. Parker, W.B.; White, E.L.; Shaddix, S.C.; Ross, L.J.; Buckheit, R.W., Jr.; Germany, J.M.; Secrist, J.A., III; Vince, R.; Shannon, W.H. Mechanism of inhibition of human immunodeficiency virus Type 1 reverse transcriptase and human DNA polymerases α, β, γ by the 5′-triphosphates of Carbovir, 3′-azido-3′-deoxythymidine, 2′,3′- dideoxyguanosine, and 3′-deoxythymidine. J. Biol. Chem. 1991, 266, 1754-1762.
4. Jeffrey, J.L.; Feng, J.Y.; Qi, C.C.R.; Anderson, K.S.; Furman, P.A. Dioxolane guanosine 5′-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. J. Biol. Chem. 2003, 278, 18971-18979.
5. Wagner, C.R.; Iyer, V.V.; McIntee, E.J. Pronucleotides: toward the in vivo delivery of antiviral and anticancer nucleotides. Med. Res. Rev. 2000, 20, 417-451.
6. De Clercq, E. Antiviral drugs: current state of the art. J. Clin. Virol. 2001, 22, 73-89.
7. Bayes, M.; Rabasseda, X.; Prous, J.R. Gateways to clinical trials. Methods Find Exp. Clin. Pharmacol. 2003, 25, 53-76.
8. Selmi, B.; Deval, J.; Borreto, J.; Canard, B. Nucleotide analogue binding, catalysis and primer unblocking in the mechanisms of HIV reverse transcriptase-mediated resistance to nucleoside analogues. Antivir. Ther. 2003, 8, 143-154.
9. Wang, G.; Boyle, N.; Chen, F.; Rajappan, V.; Fagan, P.; Brooks, J.L.; Hurd, T.; Leeds J.M.; Rajwanshi, V.K.; Jin, Y.; Prhavc, M.; Bruice, T.W.; Cook, P.D. Synthesis of AZT 5′-triphosphate mimics and their inhibitory effects on HIV-1 reverse transcriptases. J. Med. Chem. 2004, 47, 6902-6913.
10. Horwitz, J.P.; Chua, J.; Noel, M. Nucleosides. V. The monomesylates of 1-(2′-deoxy-β-D-lyxofuranosyl)thymine. J. Org. Chem. 1964, 29, 2076-2078.
11. Lin, T.-S.; Shen, Z.-Y.; August, E.M.; Brankovan, V.; Yang, H.; Ghazzouli, I.; Prusoff, W.H. Synthesis and antiviral activity of several 2,5′-anhydro analogs of 3′-azido-3′-deoxythymidine (AZT), 3′-azido-2′,3′-dideoxyuridine (AZU), 3′-azido-2′, 3′-dideoxy-5-halouridines, and 3′-deoxythymidine against human immunodeficiency virus (HIV-1) and Rauscher-Murine leukemia virus (R-MuLV). J. Med. Chem. 1989, 32, 1891-1895.
12. Hakimelahi, G.H.; Moosavi-Movahedi, A.A.; Sadeghi, M.M.; Tsay, S.-C.; Hwu, J.R. Design, synthesis, and structure-activity relationship of novel dinucleotide analogs as agents against herpes and human immunodeficiency viruses. J. Med. Chem. 1995, 38, 4648-4659.
13. Freeman, G.A.; Rideout, J.L.; Miller, W.H.; Reardon, J.E. 3′-Azido-3′,5′-dideoxythymidine-5′-methylphosphonic acid diphosphate: synthesis and HIV-1 reverse transcriptase inhibition. J. Med. Chem. 1992, 35, 3192-3196.
14. Krecmerova, M.; Hrebabecky, H.; Masojidkova, M.; Holy, A. 2′,3′-Dideoxy- and 3′-azido-2′,3′- dideoxynucleosides of 5-phenyl-2(1h)-pyrimidinone. Preparation of 2′,3′-dideoxypentofuranoses. Collect. Czechoslov. Chem. Commun. 1996, 61, 478-488.
15. Seville, M.; West, A.B.; Cull, M.G.; McHenry, C.S. Fluorometric assay for DNA polymerases and reverse transcriptase. BioTechniques 1996, 21, 664-672.