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 α4β2Ki 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.
| Original language | English |
|---|---|
| Pages (from-to) | 51-61 |
| Number of pages | 11 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 180 |
| DOIs | |
| Publication status | E-pub ahead of print - Jul 5 2019 |
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Novel N-aryl nicotinamide derivatives : Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors. / Murineddu, Gabriele; Gotti, Cecilia; Asproni, Battistina; Corona, Paola; Martinello, Katiuscia; Plutino, Simona; Fucile, Sergio; Temml, Veronika; Moretti, Milena; Viani, Paola; Schuster, Daniela; Piras, Sandra; Deligia, Francesco; Pinna, Gerard A.
In: European Journal of Medicinal Chemistry, Vol. 180, 05.07.2019, p. 51-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel N-aryl nicotinamide derivatives
T2 - Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors
AU - Murineddu, Gabriele
AU - Gotti, Cecilia
AU - Asproni, Battistina
AU - Corona, Paola
AU - Martinello, Katiuscia
AU - Plutino, Simona
AU - Fucile, Sergio
AU - Temml, Veronika
AU - Moretti, Milena
AU - Viani, Paola
AU - Schuster, Daniela
AU - Piras, Sandra
AU - Deligia, Francesco
AU - Pinna, Gerard A
N1 - Copyright © 2019 Elsevier Masson SAS. All rights reserved.
PY - 2019/7/5
Y1 - 2019/7/5
N2 - 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 α4β2Ki 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.
AB - 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 α4β2Ki 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.
U2 - 10.1016/j.ejmech.2019.06.079
DO - 10.1016/j.ejmech.2019.06.079
M3 - Article
VL - 180
SP - 51
EP - 61
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -