Structure–activity relationships of novel anti-malarial agents. Part 7: N-(3-Benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides with polar moieties

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 13; pp. 2159 - 2161
• Main Authors: Wiesner, Jochen, Mitsch, Andreas, Jomaa, Hassan, Schlitzer, Martin
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 07.07.2003; Elsevier
• Subjects: Acrylates - chemical synthesis; Acrylates - pharmacology; Alkyl and Aryl Transferases - antagonists & inhibitors; Amides - chemical synthesis; Amides - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Farnesyltranstransferase; Furans - chemical synthesis; Furans - pharmacology; Hydrogen Bonding; Indicators and Reagents; Medical sciences; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Structure-Activity Relationship; Protozoa; Antimalarial; Apicomplexa; Benzophenone derivatives; Five membered ring; Sulfone; Benzene derivatives; Oxygen heterocycle; Ketone; In vitro; Antiprotozoal agent; Plasmodium falciparum; Structure activity relation; Parasiticid; Vinylic compound; Carboxamide; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00353-6

In a previous report, we have provided evidence that novel anti-malarial compounds based on 2,5-diaminobenzophenone farnesyltransferase inhibitors might benefit from the presence of a polar moiety at the para position of the terminal phenyl of the arylfurylacryloyl partial structure. Here, we demonstrate that different moieties with hydrogen bond acceptor properties lead to equipotent or even improved anti-malarial activity in comparison to the nitro group described before. We have described evidence that novel anti-malarial compounds based on 2,5-diaminobenzophenone farnesyltransferase inhibitors might benefit from the presence of a polar moiety with hydrogen bond acceptor properties at the arylfurylacryloyl partial structure. Here, we demonstrate that several moieties with hydrogen bond acceptor properties lead to improved anti-malarial activity in comparison to the nitro group described before.