Synthesis of fluorine and iodine analogues of clorgyline and selective inhibition of monoamine oxidase A

A series of fluorine and iodine analogues of clorgyline was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase A (MAO-A). Among them, N-[3-(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2-propynylami ne (3d), N-[3-(4-chloro-2-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3f) and N-[3-(2-chloro-4-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3g) were found to have high inhibitory potency and selectivity toward MAO-A comparable to those of clorgyline itself. Thus, they were considered for advanced development as radiofluorinated and radioiodinated ligands that may be useful for functional MAO-A studies in the living brain with positron emission tomography and single photon emission computer tomography.