Fiche publication
Date publication
juin 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WAGNER Alain
Tous les auteurs :
Lebon F, Pegurier C, Ledecq M, Mathieu B, Bosman N, Frycia A, Lengele S, Dhurke K, Kanduluru AK, Meunier S, Wagner A, Wolff C, Provins L
Lien Pubmed
Résumé
A multi-disciplinary approach was used to identify the first pharmacophore model for KCC2 blockers: several physico-chemical studies such as XRD and NMR were combined to molecular modelling techniques, SAR analysis and synthesis of constrained analogues in order to determine a minimal conformational space regrouping few potential bioactive conformations. These conformations were further compared to the conformational space of a different series of KCC2 blockers in order to identify the common pharmacophoric features. The synthesis of more potent analogues in this second series confirmed the usefulness of this KCC2 blocker pharmacophore model.
Référence
Bioorg Med Chem Lett. 2012 Jun 15;22(12):3978-82
