RESUMO
Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosphonates 2 correlates well with the type and extent of their chemical or enzymatic degradation in culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides.
Assuntos
Fármacos Anti-HIV/síntese química , HIV/efeitos dos fármacos , Hidroxiácidos/química , Hidroxiácidos/farmacologia , Organofosfonatos/síntese química , Organofosfonatos/farmacologia , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Células Cultivadas , Humanos , Hidroxiácidos/síntese química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Replicação Viral/efeitos dos fármacos , Zidovudina/química , Zidovudina/farmacologiaRESUMO
In this paper a short account of our recent basic studies aiming toward development of new synthetic methods for the preparation of nucleotide analogues using H-phosphonate chemistry is presented.
Assuntos
Nucleotídeos/síntese química , Organofosfonatos/química , Compostos de Fósforo/síntese química , Fósforo/química , Modelos Químicos , Nucleosídeos/química , Nucleotídeos/química , EstereoisomerismoRESUMO
In this paper a short account of our recent research concerning the development of new synthetic methods and reagents for the preparation of nucleotides and their analogues, is given.
Assuntos
Nucleosídeos/química , Organofosfonatos/química , Compostos de Sulfidrila/química , Modelos Moleculares , Nucleosídeos/síntese química , Nucleotídeos/síntese química , Nucleotídeos/químicaRESUMO
[reaction: see text] Aryl nucleoside H-phosphonates 3 and aryl nucleoside P-acylphosphonates 4, generated in situ from the appropriate H-phosphonate 1 and acylphosphonate monoesters 2, respectively, reacted rapidly in the presence of tertiary amines to produce in high yields the extended, pyrophosphate analogues, diaryl dinucleoside phosphonate-phosphate derivatives 6. These, depending on a substituent on the alpha-carbon of the phosphonate moiety, either underwent transformation into the dinucleoside phosphonate-phosphate 7 or afforded nucleoside H-phosphonates 8 and aryl nucleoside phosphate 9.
