Towards a KCC2 blocker pharmacophore model
| Autor: | Ledecq Marie, Stéphane Meunier, Benoit Mathieu, Laurent Provins, Christian Wolff, Sébastien Lengelé, Alain Wagner, Anne Frycia, Florence Lebon, Nathalie Bosman, Cecile Pegurier, Kashinath Dhurke, Ananda Kumar Kanduluru |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Proline Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Biochemistry Structure-Activity Relationship X-Ray Diffraction Furosemide Cell Line Tumor Drug Discovery Potassium Channel Blockers Animals Humans Molecular Biology Ion Transport Symporters Chemistry Organic Chemistry High-Throughput Screening Assays Rats Molecular Medicine Anticonvulsants Pharmacophore |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:3978-3982 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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