STUDIES ON ANTIMALARIALS XI. SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF SOME 2, 4-DIAMINO-6-(N-SUBSTITU-TED-P-CHLOROBENZYLAMINO) QUINAZOLINE DERIVATIVES

Thirty three 2, 4-diamino-6-(N-substituted-p-chlorobenzylamino)-quinazolines were synthesized. These compounds were prepared by treatment of 2, 4-diamino-6-p-chlorobenzylamino quinazoline(Ⅰ) with acyl chloride, sulfonyl chloride, isosulfocyanate or acrylonitrile, the corresponding compounds(20～30) were obtained respectively. Some substituted amino methyl compounds(31～33) were prepared by Mannich reaction of(Ⅰ). Moreover, the nitroso derivative(5) of(Ⅰ) through reduction afforded amino-compound(14) which was condensed with the appropriate benzaldehyde to give the requisite Schiff bases(15～19).Suppressive therapeutic tests in mice infected with Plasmodium berghei showed that ten(1, 2, 5～8, 14, 20, 21, 26) out of these compounds produced 90% suppression of the parasites when administered orally at dose of 20 mg/kg/d × 3. Twenty six compounds(1～12, 14, 20～22, 24～33) given orally at dose of 5 mg/kg/d × 3 were shown to possess causal prophylactic activity against P. yoelii in mice. When the regimen was reduced to 0.625 mg/kg/d × 3 thirteen compounds(5～12, 20, 21, 26, 31, 33) were shown to prevent the test mice from being infected. In tests against P. cynomolgi in rhesus monkeys, four compounds(1, 8, 20, 25) were found to be less effective than primaquine and pyrimethamine in the same dosage level.