Solid-phase synthesis of novel inhibitors of farnesyl transferase.
A novel diphosphate mimic, the 2,3,6-trifluoro-5-hydroxy-4-nitrophenoxy group (1), has been employed as the template in the solid-phase synthesis of novel farnesyl transferase inhibitors using the Mitsunobu reaction. The most potent inhibitor (farnesyloxy-5-hydroxy-2,3,6-trifluoro-4-nitrobenzene) displayed an IC50 of 6.3 microM versus farnesyl transferase.
Barber
A M
AM
Cancer Research Campaign Laboratory, CRC Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, UK.
Hardcastle
I R
IR
Rowlands
M G
MG
Nutley
B P
BP
Marriott
J H
JH
Jarman
M
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase
D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase