Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B

N-Benzyl- and N-propargyl-1H-pyrrole-2-carboxy-amides and some related methylenamines were synthesized and tested for their monoamine oxidase types A and B inhibitory activity. 2-(N-Methyl-N-propargylaminomethyl)-1H-pyrrole (24) was the most potent MAO-A inhibitor of the series [K-i(MAO-A) = 0.0054 muM], but it was not selective. Inhibitors N-4-fluorobenzyl-1H-pyrrole-2-carboxamide (12) and N-cyclo-hexylmethyl-1H-pyrrole-2-carboxamide (25) showed the highest MAO-A selectivity indexes (SI) corresponding to 2025 and > 2500, respectively, while 2-(N-methyl-N-benzylaminomethyl)-1H-pyrrole (21) was the most selective MAO-B inhibitor, having an SI of 0.0057.