Novel N-aryl nicotinamide derivatives

Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors

Gabriele Murineddu, Cecilia Gotti, Battistina Asproni, Paola Corona, Katiuscia Martinello, Simona Plutino, Sergio Fucile, Veronika Temml, Milena Moretti, Paola Viani, Daniela Schuster, Sandra Piras, Francesco Deligia, Gerard A Pinna

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)51-61
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume180
DOIs
Publication statusE-pub ahead of print - Jul 5 2019

Fingerprint

Heptanes
Niacinamide
Cholinergic Receptors
Ligands
Derivatives
Nicotinic Receptors
Structure-Activity Relationship
Libraries

Cite this

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 journalArticle

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 2019, 'Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors', European Journal of Medicinal Chemistry, vol. 180, pp. 51-61. https://doi.org/10.1016/j.ejmech.2019.06.079
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. / Novel N-aryl nicotinamide derivatives : Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 180. pp. 51-61.
@article{342958e3f52e41629aba2d08f45d3762,
title = "Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors",
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.",
author = "Gabriele Murineddu and Cecilia Gotti and Battistina Asproni and Paola Corona and Katiuscia Martinello and Simona Plutino and Sergio Fucile and Veronika Temml and Milena Moretti and Paola Viani and Daniela Schuster and Sandra Piras and Francesco Deligia and Pinna, {Gerard A}",
note = "Copyright {\circledC} 2019 Elsevier Masson SAS. All rights reserved.",
year = "2019",
month = "7",
day = "5",
doi = "10.1016/j.ejmech.2019.06.079",
language = "English",
volume = "180",
pages = "51--61",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

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 -