Design and synthesis of bioactive adamantane spiro heterocycles.
Spiro[aziridine-2,2'-adamantanes] 1 and 2, spiro[azetidine-2,2'-adamantanes] 3 and 5, spiro[azetidine-3,2'-adamantane] 13, spiro[piperidine-4,2'-adamantanes] 25 and 27, and spiro barbituric analog 18 were synthesized and tested for their anti-influenza A virus properties and for trypanocidal activity. The effect of ring size on potency was investigated. Piperidine 25 showed significant anti-influenza A virus activity, being 12-fold more active than amantadine, about 2-fold more active than rimantadine, and 54-fold more potent than ribavirin. It also proved to be the most active of the compounds tested against bloodstream forms of the African trypanosome, Trypanosoma brucei, being 1.5 times more potent than rimantadine and at least 25 times more active than amantadine.
Kolocouris
Nicolas
N
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771 Athens, Greece. Zoidis@pharm.uoa.gr
Zoidis
Grigoris
G
Foscolos
George B
GB
Fytas
George
G
Prathalingham
S Radhika
SR
Kelly
John M
JM
Naesens
Lieve
L
De Clercq
Erik
E
D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects; D007891:Leishmania / Q000187:drug effects; D014345:Trypanosoma / Q000187:drug effects
D000981:Antiprotozoal Agents; D000998:Antiviral Agents; D006571:Heterocyclic Compounds; D000218:Adamantane