Synthesis of Antimalarials by a New Route to 4-Quinolinols, 4-Quinazolinones, and 4-Cinnolinol 1-Oxides.

摘要

Nine target compounds, six 4-(4-diethylamino-1-methylbutylamino)-3-phenylquinolines and three 4-(4-diethylamino-1-methylbutylamino)-3-phenylquinazolines and 100 intermediates were prepared and submitted for testing. All six of the quinoline antimalarials showed some evidence of activity, and four of them, containing 4-methoxy 4-unsubstituted 4-bromo and 4-nitro substituents in the 3-phenyl group were classed as active in mice, though only the methoxy derivative was classed as active at a dosage (320 mg/kg) below that at which some toxic deaths were observed. Three of the compounds, were classed as active in chicks at dosages (80, 320, and 320 mg/kg, respectively) where no toxic deaths were observed. Although all three were submitted, only one of the quinazoline antimalarials, the 6-chloro-2-phenyl derivative was tested in mice; it showed strong evidence of activity, but not quite sufficient to be classed as active.