Non-thiol farnesyltransferase inhibitors: N-(4-acylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides.
We have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of our initial lead 4f yielded several non-thiol farnesyltransferase inhibitors with improved activity. These compounds display activity in the low nanomolar range.
Kettler
Katja
K
Department für Pharmazie, Ludwig-Maximilians-Universität München, Butenandtstr, München, Germany.
Sakowski
Jacek
J
Silber
Katrin
K
Sattler
Isabel
I
Klebe
Gerhard
G
Schlitzer
Martin
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D005663:Furans; D007202:Indicators and Reagents; D009574:Nitro Compounds; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase