Structure-activity relationships of novel anti-malarial agents: part 5. N-(4-acylamino-3-benzoylphenyl)-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides.
We have developed the [5-(4-nitrophenyl)-2-furyl]acrylic acid substituted benzophenone 4g as a novel lead for anti-malarial agents. Here, we demonstrated that the acyl residue at the 2-amino group of the benzophenone core structure has to be a phenylacetic acid substructure substituted in its para-position with methyl or other substituents of similar size. The trifluoromethyl substituted derivative displayed an IC(50) of 47 nM against the multi-drug resistant Plasmodium falciparum strain Dd2.
Wiesner
Jochen
J
Biochemisches Institut der Universitätsklinik Giessen, Friedrichstrasse 24, Giessen, Germany.
Kettler
Katja
K
Sakowski
Jacek
J
Ortmann
Regina
R
Jomaa
Hassan
H
Schlitzer
Martin
M
D000179:Acrylates / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000179:Acrylates; D000962:Antimalarials; D005663:Furans; D007202:Indicators and Reagents; C476320:N-(4-acylamino-3-benzoylphenyl)-(5-(4-nitrophenyl)-2-furyl)acrylic acid amide