BMS-200475, a novel carbocyclic 2'-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 2, 1997, Pages 127-132

  Bisacchi, G S ^a   Chao, S T ^a   Bachard, C ^a   Daris, J P ^a   Innaimo, S ^a   Jacobs, G A ^a   Kocy, O ^a   Lapointe, P ^a   Martel, A ^a   Merchant, Z ^a   Slusarchyk, W A ^a   Sundeen, J E ^a   Young, M G ^a   Colonno, R ^a   Zahler, R ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; ENTECAVIR; FAMCICLOVIR; LAMIVUDINE; NUCLEOSIDE ANALOG; PENCICLOVIR;

ANTIVIRAL ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG SYNTHESIS; ENANTIOMER; HEPATITIS B VIRUS; REACTION ANALYSIS;

EID: 0031013008     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00594-X     Document Type: Article

References (28)

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4. A report on the antiherpes activity of BMS-200475 (SQ-34676) and a number of its base analogs, including the adenine, thymine, and iodouracil analogs, was communicated: Slusarchyk, W. A.; Field, A. K.; Greytok, J. A.; Taunk, P.; Toumari, A. V.; Young, M. G.; Zahler, R. Fifth International Conference on Antiviral Research, Vancouver, B.C., 1992, Abstract #102; abstract published in Antiviral Res. 1992, Suppl. 1, 17, 98.
5. A report on the antiherpes activity of BMS-200475 (SQ-34676) and a number of its base analogs, including the adenine, thymine, and iodouracil analogs, was communicated: Slusarchyk, W. A.; Field, A. K.; Greytok, J. A.; Taunk, P.; Toumari, A. V.; Young, M. G.; Zahler, R. Fifth International Conference on Antiviral Research, Vancouver, B.C., 1992, Abstract #102; abstract published in Antiviral Res. 1992, Suppl. 1, 17, 98.
6. For an example of a carbocyclic adenosine analog in which the furanose oxygen is replaced by an exocyclic methylene, see: Madhavan, G. V. B.; McGee, D. P. C.; Rydzewski, R. M.; Boehme, R.; Martin, J. C.; Prisbe, E. J. J. Med. Chem. 1988, 31, 1798.
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11. Available from the Aldrich Chemical Company. Alternatively, comparable yields can be obtained by generating sodium cyclopentadienide from cyclopentadiene and sodium hydride in THF.
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22. 2O: C, 48.81; H, 5.80; N, 23.72. Found: C, 48.81; H, 5.70; N, 23.86.
23. 2: C, 55.16; H, 5.79; N, 26.80. Found: C, 55.00; H, 5.43; N, 26.89.
24. 2O: C, 55.53; H, 6.53; N, 10.80. Found: C, 55.49; H, 6.29; N, 10.84.
25. 2O: C, 35.72; H, 3.72; N, 7.58. Found: C, 35.97; H, 3.55; N, 7.32.
26. 2O: C, 47.36; H, 5.96; N, 23.02. Found: C, 47.33; H, 5.68; N, 23.01.
27. HepG2.2.15 human liver cells, which harbor integrated HBV genomes, secrete substantial amounts of infectious HBV virus particles bearing viral DNA genomes into the medium. Antiviral effects are scored as reductions in the amount of HBV DNA present in the media after treatment of the cells with the drug for 9 days. HBV DNA is released from secreted virus particles by alkali treatment, immobilized onto membranes and quantitated by hybridization with a radiolabeled HBV DNA probe.
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