Pozdnev V F, Kirkel A Z, Kamyshanskaya N S, Axenova L N, Medvedev A E
Institute of Biomedical Chemistry, Academy of Medical Sciences, Moscow, Russia.
J Neural Transm Suppl. 1998;52:351-5. doi: 10.1007/978-3-7091-6499-0_38.
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.
合成了一系列乙二胺（EDA）的聚氨酯型衍生物，并将其作为单胺氧化酶（MAO）A和B的抑制剂进行测试。芳环的性质及其上取代基的位置对抑制活性很重要。氯苄氧基羰基-EDA衍生物对MAO-A表现出选择性抑制，其中3,4-二氯苯甲酰氧基羰基-EDA是最有效的选择性MAO-A抑制剂（IC50为4 microM）。在所研究的化合物中，3,4-二氯苄氧基羰基-EDA对MAO-A的抑制作用最强。该化合物对大鼠肝脏MAO-A的活性具有非竞争性抑制作用，Ki（斜率）值为3.6 microM，而对大鼠肝脏MAO-B的抑制作用是竞争性的，Ki（斜率）值为56 microM（未显示）。2,4-二氯苄氧基羰基-EDA也以非竞争性方式抑制大鼠肝脏MAO-A，Ki为14.6 microM。
