title: Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides.
abstract: 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.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Herdewijn
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: A
authors.initials: A
authors.lastname: Van Aerschot
authors.forename: G
authors.initials: G
authors.lastname: Janssen
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D015215:Zidovudine