RESUMEN
3-(P-Chlorobenzylidene)-5, 7-dimethyl-2, 3-dihydro-1H-cyclopenta[b]quinoline-9-(di-n-butylaminomethyl)methanol and 2-[beta-(p-chlorostyryl)]-6, 8-dimethylquinoline-4-(di-n-butylaminomethyl)methanol were synthesized from 6, -8-dimethyl-4-hydroxycarbostyril by 3, 3-dichlorination, dimethoxylation th the 3-ketal, basic hydrolysis to the glyoxal acetal, Pfitzinger condensation with cylopentanone or acetone to the 2, 3-trimethylene or 2-methylquinoline, condensation with p-ClPhCHO at the 2-methylene or 2-methyl group, hydrolysis to the 4-quinaldehyde, methylenation to the epoxide, and condensation with Bu2NH. Both were curative against P. berghei in mice. The first was the more effective: active at 10 mg/kg, completely curative at 40 mg/kg, and only mildly phototoxic in animals.
Asunto(s)
Antimaláricos/síntesis química , Quinolinas/síntesis química , Animales , Antimaláricos/uso terapéutico , Espectroscopía de Resonancia Magnética , Malaria/tratamiento farmacológico , Espectrometría de Masas , Ratones , Plasmodium berghei , Quinolinas/uso terapéutico , Estereoisomerismo , Compuestos de Vinilo/síntesis química , Compuestos de Vinilo/uso terapéuticoRESUMEN
Four 2-aryl-4-quinoline(di-n-butylaminomethyl)methanols with Br, Cl, F, or OMe in position 3 were synthesized by modifications of standard reactions. The antimalarial activity decreased with increased size of the 3-substituent. The 3-F-4',6,8-Cl3 compound was the most active (at 2.5 mg/kg) and was completely curative at 80 mg/kg against P. berghei in mice.