Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors.

Marcelo Vilches-Herrera, Juan Miranda-Sepúlveda, Marco Rebolledo-Fuentes, Angélica Fierro, Susan Lühr, Patricio Iturriaga-Vasquez, Bruce K Cassels, Miguel Reyes-Parada

Department of Chemistry, Faculty of Sciences, University of Chile, Casilla 653, Santiago, Chile.

Bioorganic & medicinal chemistry 2009 Mar 15

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A series of naphthylisopropylamine and N-benzyl-4-methylthioamphetamine derivatives were evaluated as monoamine oxidase inhibitors. Their potencies were compared with those of a series of amphetamine derivatives, to test if the increase of electron richness of the aromatic ring and overall size of the molecule might improve their potency as enzyme inhibitors. Molecular dockings were performed to gain insight regarding the binding mode of these inhibitors and rationalize their different potencies. In the case of naphthylisopropylamine derivatives, the increased electron-donating capacity and size of the aromatic moiety resulting from replacement of the phenyl ring of amphetamine derivatives by a naphthalene system resulted in more potent compounds. In the other case, extension of the arylisopropylamine molecule by N-benzylation of the amino group led to a decrease in potency as monoamine oxidase inhibitors.

Citation

Marcelo Vilches-Herrera, Juan Miranda-Sepúlveda, Marco Rebolledo-Fuentes, Angélica Fierro, Susan Lühr, Patricio Iturriaga-Vasquez, Bruce K Cassels, Miguel Reyes-Parada. Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors. Bioorganic & medicinal chemistry. 2009 Mar 15;17(6):2452-60