[Benzo[c][2,7]naphthyridine-5-yl-arylamines-phenol Mannich bases of the amodiaquine-, cycloquine- and pyronaridine-type].
2,5-Dichloro-4-methyl-benzo[c][2,7]naphthyridine (1) reacted with aromatic amines selectively by substitution at the 5-position to yield the amidines 2. The 4-aminophenol 2c could also be synthesized by cleavage of the ether 2b. The structure of 2c was proved by X-ray crystal analysis. Aminomethylation of 2c yielded the amodiaquine analogue 3. The mono- and bisaminomethylated derivatives 4 and 5 were obtained by reaction of compound 1 with phenol Mannich base hydrochlorides. Compounds 3-5 were tested in vitro for antimalarial activity using chloroquine-sensitive and resistant Plasmodium-falciparum strains. The highest activities were shown by the pyronaridine-type compounds 5a and 5b with IC50 values of approximately 200 nM.
Görlitzer
K
K
Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig. k.goerlitzer@tu-bs.de
Enge
C
C
Jones
P G
PG
Jomaa
H
H
Wiesner
J
J
D000655:Amodiaquine / Q000737:chemistry*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008352:Mannich Bases / Q000138:chemical synthesis*; D009287:Naphthyridines / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D011809:Quinones / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000962:Antimalarials; D008352:Mannich Bases; D009287:Naphthyridines; D011809:Quinones; C518432:cycloquine; D000655:Amodiaquine; C027871:pyronaridine