Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors
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.
Vilches-Herrera, Marcelo,Miranda-Sepulveda, Juan,Rebolledo-Fuentes, Marco,Fierro, Angelica,Luehr, Susan,Iturriaga-Vasquez, Patricio,Cassels, Bruce K.,Reyes-Parada, Miguel
experimental part
p. 2452 - 2460
(2009/09/08)
Synthesis of primary sec-alkylamines via nucleophilic ring-opening of N-phosphorylated aziridines
The novel ring-opening reaction of various 2-alkyl- and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridines (1) and (10) with copper-modified Grignard reagents proceeds regiospecifically at the less hindered carbon. The diethyl N-sec-alkylphosphoramidates (2) thus obtained may efficiently be converted to primary sec-alkylamine hydrochlorides (3) by refluxing with 20% hydrochloric acid. 2,3-Disubstituted N-phosphorylated aziridines except N-phosphorylated cyclohexenimine (4) do not react under the described conditions. Copper-mediated reaction of 2-phenyl-N-(diethoxyphosphoryl)aziridine (7) with Grignard reagents affords a mixture of regioisomers (8) and (9) but still with the preference of ring-opening at the carbon of lesser substitution.
Gajda, Tadeusz,Napieraj, Anna,Osowska-Pacewicka, Krystyna,Zawadzki, Stefan,Zwierzak, Andrzej
p. 4935 - 4946
(2007/10/03)
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