We designed the synthesis of a small library of 3-substituted-3,6-diazabicyclo[3.1.1]heptanes whose affinity on neuronal nicotinic receptors (nAChRs) was evaluated. Among the synthesized compounds, the 5-(3,6-diazabicyclo[3.1.1]heptane-3-yl)-N-(2-fluorophenyl)nicotinamide 43 proved to be the most interesting compound with α4β2 Ki value of 10 pM and a very high α7/α4β2 selectivity. Furthermore, compounds 35, 39 and 43 elicited a selective partial agonist activity for α4β2 nAChR subtype. Finally, in this paper we also report the conclusions on the 3,6-diazabicyclo[3.1.1]heptanes as ligands for nAChRs, resulting from our consolidated structure activity relationship (SAR) studies on this template.
Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors / G. Murineddu, C. Gotti, B. Asproni, P. Corona, K. Martinello, S. Plutino, S. Fucile, V. Temml, M. Moretti, P. Viani, D. Schuster, S. Piras, F. Deligia, G.A. Pinna. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 180(2019), pp. 51-61. [Epub ahead of print]
Titolo: | Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors |
Autori: | |
Parole Chiave: | 3,6-diazabicyclo[3.1.1]heptanes; Molecular docking; nAChRs; Partial agonists; Synthesis; Tobacco addiction; α; 4; β; 2; selectivity |
Settore Scientifico Disciplinare: | Settore BIO/14 - Farmacologia Settore BIO/10 - Biochimica |
Data di pubblicazione: | 2019 |
Rivista: | |
Tipologia: | Article (author) |
Data ahead of print / Data di stampa: | 5-lug-2019 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.ejmech.2019.06.079 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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