[Chloroquine analogues from benzofuro- and benzothieno[3,2-b]-4-pyridone-2-carboxylic acid esters].
The amides 7 were synthesized from the annulated methyl 4-pyridone-2-carboxylates 4 via the carboxylic acids 5 and their acid chlorides by reacting with the novaldiamine base 6. The alcohol 8b, obtained from DIBAH reduction of the ester 4b, was transformed to the chloromethyl derivative 9 which reacted with 6 and 18-crown-6 leading to the 2-novaldiaminomethyl-4-pyridone 10. Compound 10 was obtained with higher yield from DIBAH reduction of the amide 7b. The substances 7 and 10 were inactive when tested against the chloroquine resistant Plasmodium falciparum strain Dd2.
Gölitzer
K
K
Institut für Pharmazeutische Chemie, der Universitätsklinik Giessen, Germany. k.goerlitzer@tu-bs.de
Meyer
H
H
Jomaa
H
H
Wiesner
J
J
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D002264:Carboxylic Acids; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004351:Drug Resistance; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000187:drug effects; D011728:Pyridones; D013055:Spectrophotometry, Infrared
D000962:Antimalarials; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D011728:Pyridones; C492469:benzothieno(3,2-b)-4-pyridone-2-carboxylic acid; D002738:Chloroquine
Chloroquin-analoge aus Benzofuro- und Benzothieno[3,2-b]-4-pyridon-2-carbonsäureestern.