Structure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method.

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    Résumé

    A four-point pharmacophore of COX-2 selective inhibitors was derived from a training set of 16 compounds, using the Catalyst program. It consists of a H bond acceptor, two hydrophobic groups and an aromatic ring, in accordance with SAR data of the compounds and with topology of the COX-2 active site. This hypothesis, combined with exclusion volume spheres representing important residues of the COX-2 binding site, was used to virtually screen the Maybridge database. Eight compounds were selected for an in vitro enzymatic assay. Five of them show COX-2 inhibition close to that of nimesulide and rofecoxib, two reference COX-2 selective inhibitors. As a result, structure-based pharmacophore generation was able to identify original lead compounds, inhibiting the COX-2 isoform.
    langue originaleAnglais
    Pages (de - à)1446-1455
    Nombre de pages10
    journalEuropean Journal of Medicinal Chemistry
    Volume41
    Numéro de publication12
    Etat de la publicationPublié - 2006

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