Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors.

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Gaspar A, Reis J, Fonseca A, Milhazes N, Vina D, Uriarte E, Borges F

Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors.

Bioorg Med Chem Lett. 2011 Jan 15;21(2):707-9. doi: 10.1016/j.bmcl.2010.11.128. Epub 2010 Dec 5.

PubMed ID
21194943 [ View in PubMed
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Abstract

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-gamma-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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
IproniazidAmine oxidase [flavin-containing] BIC 50 (nM)7540N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)17N/AN/ADetails