Estimation of the lipophilicity of anti-HIV nucleoside analogues by determination of the partition coefficient and retention time on a Lichrospher 60 RP-8 HPLC column.
There is a close linear correlation between the log partition coefficient (Pa) of a series of 2'-deoxyriboside (dR), 2',3'-didehydro-3'-dideoxyriboside (ddeR), 2',3'-dideoxyriboside (ddR), 3'-fluoro-2',3'-dideoxyriboside (FddR) and 3'-azido-2',3'-dideoxyriboside (AzddR) derivatives of uracil, cytosine, thymine, guanine, adenine and 2,6-diaminopurine and their retention times (Rt) on a Lichrospher 60 RP-8 HPLC column (correlation coefficient r greater than 0.970). Within each class of compounds the following order of increasing lipophilicity was noted: dR less than ddeR less than ddR less than FddR less than AzddR. A straight-forward structure-lipophilicity relationship for both base and sugar modified purine and pyrimidine 2',3'-dideoxynucleosides could be delineated.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Cools
M
M
De Clercq
E
E
D000998:Antiviral Agents; D002851:Chromatography, High Pressure Liquid; D003853:Deoxyribonucleosides; D015224:Dideoxynucleosides; D006678:HIV / Q000187:drug effects*; D012995:Solubility
D000998:Antiviral Agents; D003853:Deoxyribonucleosides; D015224:Dideoxynucleosides