Structure-activity relationships of novel anti-malarial agents. Part 3: N-(4-acylamino-3-benzoylphenyl)-4-propoxycinnamic acid amides.
We have described 5-(4-propoxycinnamoylamino)-2-(4-tolylacetylamino)benzophenone 6e as a novel lead for anti-malarial agents. Anti-malarial activity of these 5-(4-propoxycinnamoylamino)benzophenones proved to be quite sensitive against variations of the acyl substituent at the 2-amino group. Best activity was obtained with phenylacetic acid moieties carrying small substituents in the para-position. From the para-substituents evaluated, the trifluoromethyl group yielded the most active compound (6j) in this series (IC50=120 nM). Deviations from the phenylacetic acid substructure, shifting the substituent into the ortho-position or bulkier para-substituents resulted in a significant reduction in anti-malarial activity.
Wiesner
Jochen
J
Biochemisches Institut der Universitatsklinik Giessen, Friedrichstrasse 24, D-35249, Giessen, Germany.
Kettler
Katja
K
Jomaa
Hassan
H
Schlitzer
Martin
M
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010648:Phenylacetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000577:Amides; D000962:Antimalarials; D001577:Benzophenones; D002934:Cinnamates; D010648:Phenylacetates; C025136:phenylacetic acid