Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides.
A series of base-modified pyrimidine 3'-azido-2',3'-dideoxynucleosides and 3'-substituted purine and pyrimidine 2',3'-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AzddUrd), 3'-azido-2',3'-dideoxy-5-methylcytidine (AzddMeCyd), 3'-fluoro-ddUrd (FddUrd), 3'-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxyguanosine (AzddGuo), 3'-fluoro-ddGuo (FddGuo), and 3'-fluoro-2,6-diaminopurine 2',3'-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.
Herdewijn
P
P
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Balzarini
J
J
Baba
M
M
Pauwels
R
R
Van Aerschot
A
A
Janssen
G
G
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D011684:Purine Nucleosides / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D015215:Zidovudine