- Design, synthesis and biological evaluation of lazabemide derivatives as inhibitors of monoamine oxidase
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In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B. It could be seen from the data of inhibition activity experiments in vitro, that the compound 3d was IC50 = 3.12 ± 0.05 μmol/mL of MAO-A and compound 3m was IC50 = 5.04 ± 0.06 μmol/mL. In vivo inhibition activity experiments were conducted to evaluate the inhibitory activity of compounds 3a, 3d, 3f, 3i and 3m by detecting the contents of 5-HT, NE, DA and activity of MAO-A and MAO-B in plasma and brain tissue. In vivo inhibition activity evaluation results showed that the compounds 3a, 3d, 3f, 3i and 3m had increased the contents of 5-HT, NE and DA in plasma and brain tissues. Meanwhile, the determination results activity of MAO in plasma and brain tissue showed that the compounds 3a, 3d, and 3f had a significant inhibitory effect on the activity of MAO-A, while the compounds 3i and 3m showed inhibitory effect on the activity of MAO-B. This study provided a new inhibitors for inhibiting of MAO activity.
- Zhou, Shiyang,Chen, Guangying,Huang, Gangliang
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p. 4863 - 4870
(2018/08/27)
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- PROCESS FOR PREPARING PYRIDINE-2-CARBOXAMIDES AND INTERMEDIATES THEREFOR
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A process for the preparation of pyridine-2-carboxamide compounds and intermediate compounds in the process are disclosed. The process involves reaction of a 2-cyano-5-halopyridine with 1,2-diaminoethane to produce a 2-(5-halopyridine-2-yl)-1H-imidazoline intermediate. This is followed by hydrolysis of the intermediate to produce a N-(2-aminoethyl)-5-halo-2-pyridinecarboxamide free base and, if desired, preparation of the acid addition salt thereafter.
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Page/Page column 15; 18
(2008/06/13)
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- PHARMACEUTICAL PREPARATIONS OF CRYSTALLINE LAZABEMIDE
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Pharmaceutical compositions of lazabemide HCl crystalline Form A are disclosed along with methods of their production.
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Page/Page column 10-13
(2008/06/13)
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- Ethylenediamine monoamides
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Compounds of the formula STR1 wherein R is an aromatic, 5- or 6-membered heterocyclic residue, as described herein, and their pharmaceutically usable acid addition salts are described. These compounds have interesting monoamine oxidase inhibiting properties with low toxicity and can accordingly be used for the treatment of depressive states and parkinsonism.
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