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-Cl2-C6H4CH2OCO-EDA being a most potent and selective MAO-A inhibitor (IC50 4 microM). 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 Ki (slope) value of 3.6 microM, whereas the inhibition of rat liver MAO-B was competitive with Ki (slope) value of 56 microM (not shown). 2.4-Dichlorobenzyloxycarbonyl-EDA also inhibited rat liver MAO-A in a non-competitive manner with Ki of 14.6 microM.
Pozdnev
V F
VF
Institute of Biomedical Chemistry, Academy of Medical Sciences, Moscow, Russia.
Kirkel
A Z
AZ
Kamyshanskaya
N S
NS
Axenova
L N
LN
Medvedev
A E
AE
D000818:Animals; D001921:Brain / Q000201:enzymology*; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D005029:Ethylenediamines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase