2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物抗鼠疟作用的研究

用伯氏鼠疟模型筛选了17个2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物。初步结果显示,化合物Ⅰ₄,Ⅰ₅,Ⅰ₁₀,Ⅰ₁₁和Ⅰ₁₂口服有较好抗疟作用,对正常敏感株(N)的SD₅₀为0.43～2.4mg/kg×4d,高度抗氯喹株(RC)为0.19～0.42mg/kg×4d,(NK₆₅)株为7.2～100mg/kg×4d,抗磺胺株(ORA)为11～76 mg/kg×4d。上述结果表明,该类化合物对(RC)株的疗效显著优于(N)株,但对(NK₆₅)株的疗效较差,与磺胺类药物有轻度交叉抗性。

ANTIMALARIAL ACTIVITY OF SOME 2,4-DIAMINO-6-SUBSTITUTED AMINO SULFONYL QUINAZOLINE DERIVATIVES

Seventeen 2,4-diamino-6-substituted amino sulfonyl quinazoline derivatives were tested for antimalarial activity on mice infected with several strains of Plasmodium berghei. In preliminary experiments, compounds I₄, I₅,I₁₀, I₁₁ and I₁₂ showed marked antimalarial activity. The SDs0 of these compounds against infections with N strain were 0.43～2.4 mg/kg×4d, PO; with NK₆₅ strain 7.2～100 mg/kg×4d, PO; with chloroquine resistant RC line 0.19～0.42 mg/kg×4d, PO; and with sulfonamide resistant ORA Iine 11～76 mg/kg×4d, PO.These results indicate that there is no cross resistance between these compounds and chloroquine. The RC line was shown to be more sensitive than the N strain. Some degree of cross resistance exists between these compounds and sulfonamides.