Influence of an additional 2-amino substituent of the 1-aminoethyl pharmacophore group on the potency of rimantadine against influenza virus A.
We examined whether the incorporation of a second amino group into the 1-aminoethyl pharmacophore of rimantadine 2 and into the piperidine pharmacophore of the heterocyclic rimantadine 4 was compatible with anti-influenza virus A activity. The new synthetic molecules are capable of forming two hydrogen bonds within the receptor. We identified molecules 8 and 16, bearing the adamantyl and 1,2-diaminoethyl groups, which are equipotent to rimantadine 2 bearing the adamantyl and 1-aminoethyl pharmacophore groups. Interestingly, diamino compound 16 is a 4-fold more potent inhibitor than its parent monoamino heterocyclic rimantadine 4 propably because of additional hydrogen bonding interactions with the M2 protein receptor.
Tataridis
Dimitrios
D
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou GR-15771 Athens, Greece.
Fytas
George
G
Kolocouris
Antonios
A
Fytas
Christos
C
Kolocouris
Nicolas
N
Foscolos
George B
GB
Padalko
Elizaveta
E
Neyts
Johan
J
De Clercq
Erik
E
D000586:Amination; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D007202:Indicators and Reagents; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D012299:Rimantadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication
D000998:Antiviral Agents; D007202:Indicators and Reagents; D012299:Rimantadine