Design and synthesis of bioactive adamantanaminoalcohols and adamantanamines.
Adamantanamines 16, 18, 21, 24, 27, 28, 30, 32, 35, 36, 37, 40, 46 and 48 were synthesized and tested for anti-influenza A virus and trypanocidal activity. The stereoelectronic requirements for optimal antiviral and trypanocidal potency were investigated. The effect of introducing a hydroxyl group close to the amino group on this class of compounds was examined for the first time. Aminoalcohol 24 proved to be the most active of the compounds tested against influenza A virus, being 6-fold more active than amantadine, equipotent to rimantadine and 26-fold more potent than ribavirin. Aminoalcohols 36 and 37 were found to have considerable activity against bloodstream forms of the African trypanosome, Trypanosoma brucei, being almost 10 times more potent than rimantadine.
Zoidis
Grigoris
G
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771 Athens, Greece.
Kolocouris
Nicolas
N
Kelly
John M
JM
Prathalingam
S Radhika
SR
Naesens
Lieve
L
De Clercq
Erik
E
D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000438:Alcohols / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D009980:Influenza A virus / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared; D014346:Trypanosoma brucei brucei / Q000187:drug effects
D000438:Alcohols; D000588:Amines; D000998:Antiviral Agents; D000218:Adamantane