Novel N-aryl nicotinamide derivatives: Taking stock on 3,6-diazabicyclo[3.1.1]heptanes as ligands for neuronal acetylcholine receptors

Autor:	Gabriele Murineddu, Sandra Piras, Veronika Temml, Daniela Schuster, Battistina Asproni, Katiuscia Martinello, Gérard Aimé Pinna, Paola Viani, Sergio Fucile, Paola Corona, Milena Moretti, Simona Plutino, Cecilia Gotti, Francesco Deligia
Rok vydání:	2019
Předmět:	Niacinamide alpha(4)beta(2) selectivity nAChRs Stereochemistry α4β2 nachr Partial agonists Receptors Nicotinic Ligands 01 natural sciences Partial agonist 6-diazabicyclo[3.1.1]heptanes Cell Line Structure-Activity Relationship Synthesis 03 medical and health sciences chemistry.chemical_compound Drug Discovery Humans Structure–activity relationship Nicotinic Agonists 030304 developmental biology Acetylcholine receptor Neurons Pharmacology 0303 health sciences Dose-Response Relationship Drug Molecular Structure Nicotinamide Nicotinic Receptors 3 6-diazabicyclo[3.1.1]heptanes Tobacco addiction Molecular docking 010405 organic chemistry Aryl Organic Chemistry General Medicine 0104 chemical sciences Molecular Docking Simulation chemistry Selectivity Azabicyclo Compounds
Zdroj:	European Journal of Medicinal Chemistry. 180:51-61
ISSN:	0223-5234
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5fc9db866b3fa9bbd9968942b6d81b72 https://doi.org/10.1016/j.ejmech.2019.06.079 Zobrazit plný text záznamu Full Text from ScienceDirect