Non-thiol farnesyltransferase inhibitors: N-(4-Acylamino-3-benzoylphenyl)-4-nitrocinnamic acid amides.
We have developed the 4-nitrocinnamoyl substituted benzophenone 4a as a novel non-thiol farnesyltransferase inhibitor. Replacement of the p-tolyl moiety of our initial lead structure 4a by different para and ortho substituted phenyl residues as well as by 1-naphthyl resulted in derivatives with considerably enhanced activity displaying IC(50) values between 42 and 52 nM. These compounds represent novel, readily accessible non-thiol farnesyltransferase inhibitors being more active than the corresponding thiol-containing analogues.
Sakowski
Jacek
J
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, D-35032, Marburg, Germany.
Sattler
Isabel
I
Schlitzer
Martin
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000737:chemistry; D001577:Benzophenones / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000577:Amides; D001577:Benzophenones; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase