Details

Autor(en) / Beteiligte

• Matos, Maria João
• Viña, Dolores
• Janeiro, Patricia
• Borges, Fernanda
• Santana, Lourdes
• Uriarte, Eugenio

Titel

New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2010-09, Vol.20 (17), p.5157-5160

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2010

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• New series of bromo-6-methyl-3-phenylcoumarin derivatives, with bromo atom in both different benzene rings of the skeleton, and with or without different number of methoxy substituent at the 3-phenyl ring, were synthesized. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3– 7 were evaluated as MAO-A and B inhibitors. With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the synthesis and pharmacological evaluation of a new series of bromo-6-methyl-3-phenylcoumarin derivatives (with bromo atom in both different benzene rings of the skeleton) with and without different number of methoxy substituent at the 3-phenyl ring. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3– 7 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 low nanomolar range. Compounds 4 (IC 50 = 11.05 nM), 5 (IC 50 = 3.23 nM) and 6 (IC 50 = 7.12 nM) show higher activity than selegiline (IC 50 = 19.60 nM) and higher MAO-B selectivity, with more than 9050-fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform.