Design, synthesis, and trypanocidal activity of new aminoadamantane derivatives.
To develop functionalized adamantanes for treating African trypanosomiasis, we report on the synthesis of new 1-alkyl-2-aminoadamantanes 1a- i, 1-alkyltricyclo[3.3.1.1 (3,7)]decan-2-guanylhydrazones 2a- g, and their congeneric thiosemicarbazones 3a, b. The potency of these compounds against Trypanosoma brucei was compared to that of amantadine and rimantadine and found to be substantially higher. The most active analogues, 1c, 1d, 2c, 2g, and 3b, illustrate the synergistic effect of the lipophilic character of the C1 side chain and the C2 functionality on trypanocidal activity.
Papanastasiou
Ioannis
I
Department of Pharmaceutical Chemistry, University of Athens, Athens, Greece.
Tsotinis
Andrew
A
Kolocouris
Nicolas
N
Prathalingam
S Radhika
SR
Kelly
John M
JM
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D021261:Parasitic Sensitivity Tests; D012299:Rimantadine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D014344:Trypanocidal Agents; D012299:Rimantadine; D000547:Amantadine; D000218:Adamantane