Non-thiol farnesyltransferase inhibitors: structure-activity relationships of aralkylsubstituted benzophenones.
We describe a novel class of benzophenone-based farnesyltransferase inhibitors exploiting a novel aryl binding region in the farnesyltransferase's active site. The present study was mainly focussed on structural modifications of the trimethylene spacer of the 4-phenyl butyroyl residue of our lead structure (IC50 = 530 nM). These modifications turned out to have little effect on activity as had the replacement of the terminal aryl by cyclohexyl (IC50 = 440 nM vs. IC50 = 530 nM).
Mitsch
A
A
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.
Wissner
P
P
Sattler
I
I
Schlitzer
M
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D001577:Benzophenones / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D013329:Structure-Activity Relationship
D001577:Benzophenones; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase