[[1]Benzothieno[3,2-b]pyridin-4-yl-amine--synthesis and investigation of activity against malaria].
The ethyl 4-chlorobenzothieno[3,2-b]pyridine-3-carboxylate (2) reacted with the hydrochlorides of the mono- and bis-phenol Mannich bases 6 to yield the amodiaquine and pyronaridine analogues 9. The chloroquine analogue 10 was formed by melting 2 with the novaldiamine base (7) in phenol. The stability of the 4-aminophenols 9 was investigated by anodic oxidation using the rotating platinum electrode by means of difference pulse voltammetry. The half wave potentials were measured giving E(1/2) approximately 1.05 V. Compound 9g displayed the highest activity against the growth of the malaria parasite Plasmodium falciparum. Testing against the chloroquine sensitive 3D7 and the chloroquine resistant Dd2 strain resulted in IC50 values of 150 nM and 210 nM, respectively. Surprisingly, the 3-carbinol 4 and the 3-chloromethyl derivative 5, synthesized from the 3-carboxylic acid ester 2, reacted with the phenol Mannich base 6a and the novaldiamine base (7), respectively, to yield the 4-pyridone 8.
Institut für Pharmazeutische Chemie, der Universitätsklinik GieBen, Germany. k.goerlitzer@tu-bs.de
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K
Görlitzer
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H
Meyer
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RD
Walter
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H
Jomaa
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Wiesner
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004563:Electrochemistry; D007202:Indicators and Reagents; D008352:Mannich Bases; D010963:Plasmodium falciparum / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000588:Amines; D000962:Antimalarials; D007202:Indicators and Reagents; D008352:Mannich Bases; D011725:Pyridines; D002738:Chloroquine