Non-thiol farnesyltransferase inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic acid amides.
We have designed arylfurylacryl-substituted benzophenones as non-thiol farnesyltransferase inhibitors utilizing a novel aryl binding site of farnesyltransferase. These compounds display activity in the low nanomolar range.
Mitsch
Andreas
A
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.
Wissner
Pia
P
Silber
Katrin
K
Haebel
Peter
P
Sattler
Isabel
I
Klebe
Gerhard
G
Schlitzer
Martin
M
D000179:Acrylates / Q000138:chemical synthesis* / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D020128:Inhibitory Concentration 50; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000179:Acrylates; D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase