Antimalarial and anticoccidial activity of 3-aryl-7-chloro-3,4-dihydroacridine-1,9-(2H,10H)-diones. 1-Imines, 1-amines, 1-oximes, 1-hydrazones and related compounds.
Out of more than 130 synthesized derivatives of floxacrine and of 10-deoxyfloxacrine, such as 3-(4-trifluoromethyl-phenyl) or 3-(4-chlorophenyl)-7-chloro-10-hydroxy- or -10-deoxy-3,4-dihydroacridine- 1,9(2H,10H)-dione 1-imines and 1-hydrazones, more than 45 showed an activity against asexual stages of Plasmodium berghei in the mouse which was comparable with or superior to that of floxacrine. More than 25 derivatives of the 3-(4-chlorophenyl)-floxacrine series and 3-(4-chlorophenyl)-10-deoxy-floxacrine series are more effective than floxacrine against Eimeria tenella infection in chickens. 1-Amino compounds of the various series proved of be generally inactive, as did fragments of the structure of and compounds related to floxacrine. Structure-activity relations are suggested on the basis of examples.
Winkelmann
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Department of Drug Synthesis, Hoechst Aktiengesellschaft, Frankfurt/Main, Fed. Rep. of Germany.
Raether
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W
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D003049:Coccidiostats / Q000138:chemical synthesis*; D004539:Eimeria / Q000187:drug effects; D005260:Female; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology; D007097:Imines / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051379:Mice; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship
D000166:Acridines; D000588:Amines; D000962:Antimalarials; D003049:Coccidiostats; D006835:Hydrazones; D007097:Imines; D010091:Oximes; C022008:floxacrine