Novel inhibitors of the prenylated protein methyltransferase reveal distinctive structural requirements

Inhibitors of a prenylated protein methyltransferase were synthesized and evaluated. S-farnesyl-5-fluorothiosalicylic acid and the 5-chloro analog (but not the 4-fluoro, 4-chloro or 3-chloro analogs) were potent inhibitors, as was the parent compound S-farnesyl thiosalicylic acid (FTS), whose methyl ester was far less active. S-geranyl and S-geranylgeranyl thiosalicylic acids were more than ten times less potent than FTS.