Inhibition of Human Immunodeficiency Virus Reverse Transcriptase by Synadenol Triphosphate and Its E-Isomer

Journal of Medicinal Chemistry

Volumn 46, Issue 22, 2003, Pages 4799-4802

  Wang, Ruifang ^a   Harada, Shigeyoshi ^b   Mitsuya, Hiroaki ^b,c   Zemlicka, Jiri ^a  

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

^b KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MUTANT PROTEIN; RNA DIRECTED DNA POLYMERASE; SYNADENOL; SYNADENOL TRIPHOSPHATE; UNCLASSIFIED DRUG;

ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; HUMAN IMMUNODEFICIENCY VIRUS; ISOMER; NONHUMAN;

ANTI-HIV AGENTS; HIV-1 REVERSE TRANSCRIPTASE; MUTATION; NUCLEOSIDES; REVERSE TRANSCRIPTASE INHIBITORS; STEREOISOMERISM;

EID: 0142124180     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030048y     Document Type: Article

References (15)

1. Qiu Y.-L.; Ksebati, M. B.; Ptak, R. G.; Fan, B. Y.; 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.; Kern, E. R.; Drach, J. C.; Zemlicka, J. (Z)- and (E)-(2-Hydroxymethyl)cyclopropylidenemethylpurines and Pyrimidines as Antiviral Agents. Antiviral Chem. Chemother. 1998, 9, 341-52.
3. Uchida, H.; Kodama, E. N.; Yoshimura, K.; Maeda, Y.; Kosalaraksa, P.; Maroun, V.; Qiu Y.-L.; Zemlicka, J.; Mitsuya, H. In Vitro Anti-Human Immunodeficiency Virus Activities of Z- and E-Methylenecyclopropane Nucleoside Analogues and their Phosphoro-L-alaninate Diesters. Antimicrob. Agents Chemother: 1999, 43, 1487-1490.
4. Cheng, C.; Shimo, T. Somekawa, K.; Somekawa, K.; Baba, M. 9-Hydroxymethyl-cyclopropylidene-methylenyladenine: The Design, Facile Synthesis, Isomer Separation and Anti-HIV-1 Activities. Tetrahedron 1998, 54, 2031-2040.
5. Qiu, Y.-L.; Ptak, R. G.; Breitenbach, J. M.; Lin, J.-S.; Cheng, Y.-C.; Drach, J. C.; Kern, E. R.; Zemlicka, J. Synthesis and Antiviral Activity of Phosphoralaninate Derivatives of Methylenecyclopropane Analogues of Nucleosides. Antiviral Res. 1999, 43, 37-53.
6. Zemlicka, J. Lipophilic phosphoramidates as antiviral pronucleotides. Biochim. Biophys. Acta (Molecular Basis of Disease) 2002, 1587, 276-286.
7. Tanaka, H.; Baba, M.; Saito, S.; Miyasaka, T.; Takashima, H.; Sekiya, K. ; Ubasawa, M.; Nitta, I.; Walker, R. T.; Nakashima, H.; De Clercq, E. Specific Anti-HIV-1 "Acyclonucleosides" which Cannot be Phosphorylated: Synthesis of Some Deoxy Analogues of 1-[(2-Hydroxy-ethoxy)methyl]-6-(phenylthio)thymine. J. Med. Chem. 1991, 34, 1508-1511.
8. Buckheit, R. W., Jr.; Turpin, J. A.Mechanisms of anti-HIV Action of SJ-3366: Effects on Reverse Transcriptase and Cell Surface Events. Antiviral Res. 2001, 51, 2-3.
9. Orr, D. C.; Figueiredo, H. T.; Mo, C.-L.; Penn, C. R.; Cameron, J. M. DNA Chain Termination Activity and Inhibition of Human Immunodeficiency Virus Reverse Transcriptase by Carbocyclic 2′,3′-Didehydro-2′ ,3′-dideoxyguanosine Triphosphate. J. Biol. Chem. 1992, 267, 4177-4182.
10. Qiu, Y.-L.; J. Zemlicka, J. 3,5′-Anhydrosynadenol: a Polycyclic Anhydronucleoside Analogue. Angew. Chem., Int. Ed. 1998, 37, 1440-1441.
11. Wang, R.; Corbett, T. H.; Cheng, Y.-C.; Drach, J. C.; Kern, E. R.; Mitsuya, H.; Zemlicka, J. Tryptophanyl Phosphoramidates as Prodrugs of Synadenol and its E-Isomer: Synthesis and Biological Activity. Bioorg. Med. Chem. Lett. 2002, 12, 2467-2470.
12. Johnson, M. A.; Ahluwalia, G.; Connelly, M. C.; Cooney, D. A.; Broder, S.; Johns, D. G.; Fridland, A. Metabolic Pathways for the Activation of the Antiretroviral Agent 2′,3′-Dideoxyadenosine in Human Lymphoid Cells. J. Biol. Chem. 1988, 263, 15354-15357.
13. Saboulard, D.; Naesens, L.; Cahard, D.; Salgado, A.; Pathirana, R.; Velasquez, S.; McGuigan, C.; De Clercq, E.; Balzarini, J. Characterization of the Activation Pathway of Phosphoramidate Triester Prodrugs of Stavudine and Zidovudine. Mol. Pharmacol. 1999, 56, 693-704.
14. Yoshimura, K.; Feldman, R.; Kodama, E.; Kavlick, M. F.; Qiu, Y.-L.; Zemlicka, J.; Mitsuya, H. In Vitro Induction of Human Immunodeficiency Virus Type 1 Variants Resistant to Phosphoralaninate Prodrugs of Z-Methylenecyclopropane Nucleoside Analogues. Antimicrob. Agents Chemother. 1999, 43, 2479-2483.
15. Ueno, T.; Shirasaka, T.; Mitsuya, H.Enzymatic Characterization of Human Immunodeficiency Virus Type I Reverse Transcriptase Resistant to Multiple 2′,3′-Dideoxynucleoside 5′-Triphosphates. J. Biol. Chem. 1995, 270, 23605-23611.