Preparation and biological activity of new substituted antimalarial diaminodiphenylsulfones.
Starting from 4,4'-diamino-diphenylsulfone (DDS) as a lead structure, new 2-substituted analogues as well as new 2-substituted 4-alkylamino-4'-amino diphenylsulfones have been designed and synthetized in different ways. This has led to compounds the inhibitory activity of which against 7,8-dihydropteroic acid synthase of plasmodia and mycobacteria is clearly superior to that of sulfadoxine and in most cases to that of DDS. Of special interest is 4'-amino-4-n-propylamino-2-methyl-diphenylsulfone. Together with inhibitors of 7,8-dihydrofolate reductase in vitro and in vivo it possesses a marked synergistic inhibitory activity against plasmodia. In contrast to DDS in doses up to 200 mg/kg p.o. (cat) no methemoglobin formation is observed. The compound has been selected for further studies.
Pieper
H
H
Department of Chemical Research, Biberach an der Riss, Fed. Rep. of Germany.
Seydel
J K
JK
Krüger
G
G
Noll
K
K
Keck
J
J
Wiese
M
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D002474:Cell-Free System; D055598:Chemical Phenomena; D002621:Chemistry; D003622:Dapsone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D009161:Mycobacterium / Q000187:drug effects; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship
D000962:Antimalarials; C061807:4'-amino-4-n-propylamino-2-methyldiphenylsulfone; D003622:Dapsone