Novel amodiaquine congeners as potent antimalarial agents.
To develop new classes of antimalarial agents, the possibility of replacing the phenolic ring of amodiaquine, tebuquine, and isoquine with other aromatic nuclei was investigated. Within a first set of pyrrole analogues, several compounds displayed high activity against both D10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. The isoquine structure was also modified by replacing the diethylamino group with more metabolically stable bicyclic moieties and by replacing the aromatic hydroxyl function with a chlorine atom. Among these compounds, two quinolizidinylmethylamino derivatives (6f and 7f) displayed high activity against both CQ-S and CQ-R strains.
Casagrande
Manolo
M
Istituto di Chimica Farmaceutica e Tossicologica 'Pietro Pratesi', University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Basilico
Nicoletta
N
Parapini
Silvia
S
Romeo
Sergio
S
Taramelli
Donatella
D
Sparatore
Anna
A
D000634:Aminoquinolines; D000655:Amodiaquine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D011758:Pyrroles; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D011758:Pyrroles; D000655:Amodiaquine; C044651:tebuquine