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Novel imidazoline compounds as partial or full agonists of D2-like dopamine receptors inspired by I2-imidazoline binding sites ligand 2-BFI
Authors:Gianfabio Giorgioni  Dario Ambrosini  Cristian Vesprini  Alan Hudson  Cinzia Nasuti  Antonio Di Stefano  Piera Sozio  Osele Ciampi  Barbara Costa  Claudia Martini  Antonio Carrieri  Giuseppe Carbonara  Christoph Enzensperger  Maria Pigini
Institution:1. Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, via Sant’Agostino 1, 62032 Camerino, Italy;2. Department of Pharmacology, 9-70 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7;3. Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, via Madonna delle Carceri, 62032 Camerino, Italy;4. Dipartimento di Scienze del Farmaco, Università ‘G. D’Annunzio’, via dei Vestini, 66100 Chieti, Italy;5. Department of Human Morphology and Applied Biology, University of Pisa, via Volta 4, 56126 Pisa, Italy;6. Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, via Bonanno, 6-56126 Pisa, Italy;7. Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via E. Orabona 4, 70125 Bari, Italy;8. Friedrich-Schiller Universiät Jena, Institut für Pharmazie, Philosophenweg 14 D-07745 Jena, Germany
Abstract:Based on the well known biological versatility of the imidazoline nucleus, we prepared the novel derivatives 3ak inspired by 2-BFI scaffold to assess imidazoline molecules as D2-like dopamine receptor ligands. Conservative chemical modifications of the lead structure, such as the introduction of an hydroxy group in the aromatic ring alone or associated with N-benzyl substitution, provided partial (3f) or nearly full (3e and 3h) agonists, all endowed with D2-like potency comparable to that of dopamine.
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