疟疾治疗药物——4-芳胺基-2-特丁胺甲基酚类化合物的合成

世界许多地区,由于恶性疟原虫对氯喹已产生抗药性,因此,迫切需要寻找高效、速效、低毒与氯喹无交叉抗药性的新药。Schmidt报道将2-二乙胺甲基-4-特丁基-6-苯基苯酚(Ⅰ_a)中的二乙胺基改为特丁胺基,同时于6-苯基的对位引入氯原子,即化合物(Ⅰ_a),对多种

STUDIES ON ANTIMALARIALS SYNTHESIS OF 4-ARYLAMINO-TERT-BUTYLAMINOMETHYL PHENOLS

Six Compounds of 4-arylamino-2-tert-butylaminomethyl phenols have been synthesized and screened for activity against established infections with chloroquine sensitive strain and chloroquine-resistant strains of P. Berghei in mice. All compounds exhibited marked antimalarial effect except compound Ⅳ_c. Two of these compounds, 4-(7-chloro-4-quinolinylamino)-2-tert-butylaminomethyl-5, 6, 7, 8-tetra-hydro-1-naphthol (compound Ⅳ_a,) and 4-(2-methoxy-7-chloro-10-benzo-[b]-1, 5-naphthyridinylamino)-2-tert-butyl-amino-o-cresol (compound Ⅴ_c)were more effective than the remaining four. The ED₅₀ of compound Ⅳ_a against infections with chloroquine sensitive strain of P. Berghei was 0.33 mg/kg subcutaneously; the ED₅₀ of compound Ⅴ_c against infections with chloroquine resistant strain was 1.5 mg/kg. However, the ED₅₀ of chloroquine were 1.12 and 34.5 mg/kg respectively against the 2 strains of P Berghei. Systemetical study of these compounds are in progress.