[Benzo[c][2,7]naphthyridine-2-yl-, 5-yl- and 2,5-diyl novaldiamines--synthesis and investigation of anti-malarial activity].
The 2,5-dichlorobenzo[c][2,7]naphthyridine 6 was synthesized starting from the 2-pyridone 1 in four or five steps, respectively. The 5-yl amine 7 and the 2,5-diyl amines 8 and 9 were isolated by the reaction of compound 6 with the novaldiamine base. Starting with the reaction of the 6-chloropyridine 3 with the novaldiamine base to yield the 6-aminopyridine 11, the 2-yl amine 13, isomeric to 7, was obtained. Compounds 7-13 were tested for in vitro antimalarial activity using a chloroquine sensitive and resistant Plasmodium falciparum strain. The highest activity was shown by 8 with IC50 values of 90 nM and 190 nM, respectively.
Görlitzer
K
K
Institut für Pharmazeutische Chemiel der Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Enge
C H
CH
Jones
P G
PG
Jomaa
H
H
Wiesner
J
J
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D008968:Molecular Conformation; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000962:Antimalarials; D007202:Indicators and Reagents; D009287:Naphthyridines; D002738:Chloroquine