Synthesis and antiviral activity of N⁹-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N⁶-substituted adenines and 2,6-diaminopurines

An efficient method for the synthesis of N⁹-[3-fluoro-2-(phosphonomethoxy)propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N⁶-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HI...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2011-04, Vol.19 (7), p.2114-2124
Hauptverfasser: Baszczyňski, Ondřej, Jansa, Petr, Dračínský, Martin, Klepetářová, Blanka, Holý, Antonín, Votruba, Ivan, Clercq, Erik de, Balzarini, Jan, Janeba, Zlatko
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Sprache:eng
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Zusammenfassung:An efficient method for the synthesis of N⁹-[3-fluoro-2-(phosphonomethoxy)propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N⁶-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HIV) and anti-Moloney murine sarcoma virus (MSV) activity was evaluated. Whereas none of the 6-substituted FPMPA derivatives showed any antiviral activity, several FPMPDAP derivatives had a moderate antiretroviral activity. Moreover, the data obtained from the study of the substrate activity of the active derivatives towards N⁶-methyl-AMP aminohydrolase support the notion that the studied N⁶-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2011.02.050