[Thieno[2,3-c]quinolines - synthesis and biological investigation].
pH-Dependant reduction of the methyl 3-(2-nitrophenyl)thiophene-2-carboxylate (3), obtained by Suzuki cross-coupling of the methyl 3-iodothiophene-2-carboxylate with 2-nitrophenyl boronic acid yields the cyclic hydroxamic acid 4 and the lactam 5, respectively. The lactam 5 is also formed by reacting the compound 2 with pinacolato 2-aminophenylboronate. The 4-chlorothieno[2,3-c]quinoline 6 is formed from the lactam 5 by heating with POCl3/PCl5. Melting of 6 with the novaldiamine base in phenol gives the chloroquine analogue 7, whereas the amodiaquine and the cycloquine analogues 8 and 9 are obtained using phenol Mannich bases. The hydroxamic acid 4 has a moderate effect on eicosanoid biosynthesis in human whole blood. The growth of the chloroquine resistent Plasmodium falciparum strain Dd2 is inhibited by the pyronaridine derivative 9 with an IC50 value of 650 nM.
Görlitzer
K
K
Institut für Pharmazeutische Chemie der Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Gabriel
B
B
Frohberg
P
P
Wobst
I
I
Drutkowski
G
G
Wiesner
J
J
Jomaa
H
H
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D015777:Eicosanoids / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000494:pharmacology; D007202:Indicators and Reagents; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology; D008352:Mannich Bases; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000962:Antimalarials; D015777:Eicosanoids; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D007769:Lactams; D008352:Mannich Bases; D011804:Quinolines