title: Synthesis and antiviral activity of metabolites of rimantadine.
abstract: The hydroxy metabolites of rimantadine (3-5) were synthesized and compared to amantadine (1) and rimantadine (2) for their ability to inhibit the replication of influenza viruses in vitro. All three metabolites were inhibitory to wild-type influenza A viruses (H3N2 and H1N1). In particular, 2-hydroxyrimantadine (3) showed similar activity to amantadine, but the 3- and 4-hydroxy metabolites (4 and 5, respectively), both of which are found in rimantadine-treated patients, showed only modest inhibitory activity. A rimantadine-resistant isolate of influenza A virus exhibited cross-resistance to amantadine and to each of the metabolites 3-5. None of the compounds were effective against influenza B virus.
authors.affiliation: Department of Chemistry Research, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: P S
authors.initials: PS
authors.lastname: Manchand
authors.forename: R L
authors.initials: RL
authors.lastname: Cerruti
authors.forename: J A
authors.initials: JA
authors.lastname: Martin
authors.forename: C H
authors.initials: CH
authors.lastname: Hill
authors.forename: J H
authors.initials: JH
authors.lastname: Merrett
authors.forename: E
authors.initials: E
authors.lastname: Keech
authors.forename: R B
authors.initials: RB
authors.lastname: Belshe
authors.forename: E V
authors.initials: EV
authors.lastname: Connell
authors.forename: I S
authors.initials: IS
authors.lastname: Sim
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D012299:Rimantadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007202:Indicators and Reagents; D012299:Rimantadine; D000218:Adamantane