[Thieno[3,4-c]quinoline-4-yl-amines--synthesis and investigation of activity against malaria].
The 4-aryl derivative 3, obtained by Suzuki cross coupling of the methyl 4-bromothiophene-3-carboxylate (2) with 2-nitrophenylboronic acid cyclizes under reductive conditions pH-dependant to yield the tricyclic hydroxamic acid 4 or the lactam 5. The chlorothieno[3,4-c]quinoline 6 was formed by reaction of the lactam 5 with P,P-dichlorophenylphosphinoxide. The amines 7-14 were synthesized from the chloroimine 6. Compounds 7a,b, 8, 9, 10b, 11, 12 and 14a, b were tested for in vitro antimalarial activity using the chloroquine sensitive 3D7 and the chloroquine resistant Plasmodium falciparum strain Dd2. The highest activity were shown by 10b with IC50 values of 130 nM and 50 nM, respectively and by 11 with IC50 values of 190 nM and 44 nM, respectively.
Görlitzer
K
K
Institut für Pharmazeutische Chemie der Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Gabriel
B
B
Jomaa
H
H
Wiesner
J
J
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D000634:Aminoquinolines; D000962:Antimalarials; D007202:Indicators and Reagents; D013876:Thiophenes