<i>S</i>-Farnesyl-Thiopropionic Acid Triazoles as Potent Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase

We report the design and synthesis of novel FTPA-triazole compounds as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt), through a focus on thioether and isoprenoid mimetics. These mimetics were coupled utilizing a copper-assisted cycloaddition to assemble the potential inhibitors. Using the resulting triazole from the coupling as an isoprenyl mimetic resulted in the biphenyl-substituted FTPA triazole <b>10n</b>. This lipid-modified analogue is a potent inhibitor of Icmt (IC₅₀ = 0.8 ± 0.1 μM; calculated <i>K</i>_i = 0.4 μM)