Synthesis and Evaluation of a Set of Para-Substituted 4-Phenylpiperidines and 4-Phenylpiperazines as Monoamine Oxidase (MAO) Inhibitors
| Autor: | Susanna Waters, Nicholas Waters, Fredrik Pettersson, Peder Svensson, Clas Sonesson |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Monoamine Oxidase Inhibitors 3 4-Dihydroxyphenylacetic acid Stereochemistry Monoamine oxidase Dopamine Striatum Piperazines Structure-Activity Relationship chemistry.chemical_compound Piperidines Catalytic Domain Drug Discovery Benzene Derivatives medicine Animals Humans Structure–activity relationship Monoamine Oxidase biology Chemistry Corpus Striatum Rats Isoenzymes Monoamine neurotransmitter biology.protein 3 4-Dihydroxyphenylacetic Acid Molecular Medicine Monoamine oxidase B Monoamine oxidase A medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 55:3242-3249 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm201692d |
| Popis: | A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole moment increased the affinity to MAO A, whereas groups with high dipole moment yielded compounds with no or weak affinity. In contrast, the properties affecting MAO B affinity were the polarity and bulk of the para-substituent, with large hydrophobic substituents producing compounds with high MAO B affinity. In addition, these compounds were tested in freely moving rats and the effect on the post-mortem neurochemistry was measured. A linear correlation was demonstrated between the affinity for MAO A, but not MAO B, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum. |
| Databáze: | OpenAIRE |
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