期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 20, 期 17, 页码 5157-5160出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.07.013
关键词
Phenylcoumarins; MAOIs; Halogenation; Perkin reaction; Bromo coumarin derivatives
资金
- Spanish Ministry [PS0900501]
- Xunta da Galicia [PGIDIT09CSA030203PR, INCITE09E2R203035ES]
- FCT [PTDC/QUI/70359/2006, SFRH/BD/61262/2009]
- Fundação para a Ciência e a Tecnologia [PTDC/QUI/70359/2006] Funding Source: FCT
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 (IC50 = 11.05 nM), 5 (IC50 = 3.23 nM) and 6 (IC50 = 7.12 nM) show higher activity than selegiline (IC50 = 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. (C) 2010 Elsevier Ltd. All rights reserved.
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