Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors
| Autor: | Dolores Viña, André Fonseca, Joana Reis, Eugenio Uriarte, Nuno Milhazes, Alexandra Gaspar, Fernanda Borges |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Monoamine Oxidase Inhibitors Monoamine oxidase medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Context (language use) Carboxamide Biochemistry Chemical synthesis Cell Line Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Humans Protein Isoforms Monoamine Oxidase Molecular Biology Bicyclic molecule biology Organic Chemistry Neurodegenerative Diseases chemistry Chromones Enzyme inhibitor Chromone biology.protein Molecular Medicine Monoamine oxidase B |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:707-709 |
| ISSN: | 0960-894X |
| Popis: | Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds 2-6 and 8-12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to hMAO-B, with compounds 9 and 12 displaying IC 50 values at nanomolar range. © 2010 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect