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

  • Bioorg Med Chem. 2011 Apr 1;19(7):2114-24. doi: 10.1016/j.bmc.2011.02.050.
Ondřej Baszczyňski  1 ,  Petr Jansa ,  Martin Dračínský ,  Blanka Klepetářová ,  Antonín Holý ,  Ivan Votruba ,  Erik de Clercq ,  Jan Balzarini ,  Zlatko Janeba
Affiliations
  • 1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. Flemingovo nám. 2, 16610 Prague 6, Czech Republic.
PMID: 21429755 DOI: 10.1016/j.bmc.2011.02.050
Abstract

An efficient method for the synthesis of N(9)-[3-fluoro-2-(phosphonomethoxy)propyl] (FPMP) derivatives of purine Bases has been developed. Both (R)- and (S)-enantiomers of the N(6)-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 N(6)-methyl-AMP aminohydrolase support the notion that the studied N(6)-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues.

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