Design and synthesis of a hybrid series of potent and selective agonists of α7 nicotinic acetylcholine receptor
| Autor: | Simon N. Haydar, Jean Zhang, John Dunlop, Arianna Nencini, Laura Maccari, Elisa Turlizzi, Riccardo Zanaletti, Thomas A. Comery, Chiara Ghiron, Eva Genesio, Iolanda Micco, Cristiana Castaldo |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Models Molecular Cell Membrane Permeability alpha7 Nicotinic Acetylcholine Receptor Stereochemistry Pyrazole Structure-Activity Relationship chemistry.chemical_compound Dogs α7 nicotinic acetylcholine receptor Drug Discovery Animals Humans Urea Rats Wistar Cognitive impairment ADME Pharmacology Dose-Response Relationship Drug Molecular Structure Organic Chemistry HEK 293 cells General Medicine Rats chemistry Drug Design Pyrazoles α7 nachr |
| Zdroj: | European Journal of Medicinal Chemistry. 78:401-418 |
| ISSN: | 0223-5234 |
| Popis: | α7 nicotinic acetylcholine receptor agonists are promising therapeutic candidates for the treatment of cognitive impairment. As a follow up of our internal medicinal chemistry program we investigated a novel series of α7 nAChR agonists. Starting from molecular docking studies on two series of molecules recently developed in our laboratories, an alternative scaffold was designed attempting to combine the optimal features of these previously identified urea and pyrazole compounds. Based on our previous SAR knowledge and on predicted drug-like properties, a small library was synthesized in parallel manner, affording compounds with excellent α7 nAChR activity, selectivity and preliminary ADME profile. |
| Databáze: | OpenAIRE |
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