Abstract: With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the design, synthesis and pharmacological evaluation of a new series of 8-bromo-6-methyl-3-phenylcoumarin derivatives without substituent and with different number of methoxy substituent in the 3-phenyl ring. The substituent in this new scaffold was introduced in the 3', 4' and/or 5' positions of the 3-phenyl ring of the coumarin moiety. The synthesized compounds 3-6 were evaluated as MAO A and B inhibitors using R-(-)-deprenyl (selegiline) and Iproniazide as reference inhibitors, showing, most of them, MAO-B inhibitory activities in the nanomolar range. Compounds 3 (11.05±0.81 nM), 4 (3.23±0.49 nM) and 5 (7.12±0.01 nM) show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 9,050- fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform.