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 alpha(4)beta(2) Ki value of 10 pM and a very high alpha(7)/alpha(4)beta(2) selectivity. Furthermore, compounds 35, 39 and 43 elicited a selective partial agonist activity for alpha(4)beta(2) 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. (C) 2019 Elsevier Masson SAS. All rights reserved.
Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors / Murineddu, G; Gotti, C; Asproni, B; Corona, P; Martinello, K; Plutino, S; Fucile, S; Temml, V; Moretti, M; Viani, P; Schuster, D; Piras, S; Deligia, F; Pinna, Ga. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 180:(2019), pp. 51-61. [10.1016/j.ejmech.2019.06.079]
Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors
Plutino, SInvestigation
;Fucile, SInvestigation
;
2019
Abstract
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 alpha(4)beta(2) Ki value of 10 pM and a very high alpha(7)/alpha(4)beta(2) selectivity. Furthermore, compounds 35, 39 and 43 elicited a selective partial agonist activity for alpha(4)beta(2) 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. (C) 2019 Elsevier Masson SAS. All rights reserved.| File | Dimensione | Formato | |
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