Synthesis and biological evaluation of isomeric dinucleoside monophosphates and monomethylphosphonates of 9-beta-D-arabinofuranosyladenine and related analogues.
The 3'----5',3'----3' and 5'----5' dinucleoside monophosphates and methylphosphonates of 9-beta-D-arabinofuranosyladenine, as well as its 5'-(hydrogen phosphonate) and 5'-(methyl methylphosphonate) derivatives have been the subject of a systematic synthesis and examination of their biological, i.e. antiviral and cytostatic, properties. First the properly protected monomeric building blocks were prepared and then condensed to give fully protected intermediates. These latter were then deblocked to afford the unprotected compounds, which were fully characterized. Only the 3'----5' phosphodiester isomers 13 and 16 and, to a lesser extent, the 5'-(hydrogen phosphonate) derivative 21 showed marked biological activity.
Puech
F
F
Université des Sciences et Techniques du Languedoc, Laboratoire de Chimie Bio-Organique, U.A. 488 du CNRS, Montpellier, France.
Gosselin
G
G
qalzarini
J
J
De Clercq
E
E
Imbach
J L
JL
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D001088:Arabinonucleotides / Q000138:chemical synthesis*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D007536:Isomerism; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D001084:Vidarabine Phosphate / Q000138:chemical synthesis* / Q000494:pharmacology
D000998:Antiviral Agents; D001088:Arabinonucleotides; D011355:Prodrugs; D001084:Vidarabine Phosphate