N-Alkyloxycarbonyl derivatives of ethylene diamine as monoamine oxidase inhibitors

A series of urethane type derivatives of ethylene diamine (EDA) was synthesised and tested as inhibitors of monoamine oxidase (MAO) A and B. Nature of aromatic ring and a position of substituents in it were important for the inhibitory activity. Chlorobenzyloxycarbonyl-EDA derivatives exhibited selective inhibition of MAO-A with 3,4-Cl-2-C6H4CH2OCO-EDA being a most potent and selective MAO-A inhibitor (IC50 4 mu M). Within the compounds studied, 3,4-dichloro-benzyloxycarbonyl-EDA exhibited most potent inhibition of MAO-A. This compound inhibited the activity of rat liver MAO-A non-competitively with K-i (slope) value of 3.6 mu M, whereas the inhibition of rat liver MAO-B was competitive with K-i (slope) value of 56 mu M (not shown). 2,4-Dichlorobenzyloxycarbonyl-EDA also inhibited rat liver MAO-A in anon-competitive manner with K-i of 14.6 mu M.