Pyridinyl- and pyridazinyl-3,6-diazabicyclo[3.1.1]heptane-anilines: Novel selective ligands with subnanomolar affinity for α 4 β 2 nACh receptors.

Autor: Deligia F; Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Trav. La Crucca 3, 07100, Sassari, Italy., Murineddu G; Department of Chemistry and Pharmacy, University of Sassari, Via F. Muroni 23/A, 07100, Sassari, Italy. Electronic address: muri@uniss.it., Gotti C; CNR, Institute of Neuroscience, Via Vanvitelli 32, 20129, Milano, Italy., Ragusa G; Department of Chemistry and Pharmacy, University of Sassari, Via F. Muroni 23/A, 07100, Sassari, Italy., Fasoli F; CNR, Institute of Neuroscience, Via Vanvitelli 32, 20129, Milano, Italy., Sciaccaluga M; IRCCS Neuromed, Via Atinese 18, 86077, Pozzilli, IS, Italy., Plutino S; Dipartimento di Fisiologia e Farmacologia 'V. Erspamer, Sapienza Università di Roma, P.le Aldo Moro 5, 00185, Roma, Italy., Fucile S; IRCCS Neuromed, Via Atinese 18, 86077, Pozzilli, IS, Italy; Dipartimento di Fisiologia e Farmacologia 'V. Erspamer, Sapienza Università di Roma, P.le Aldo Moro 5, 00185, Roma, Italy., Loriga G; Institute of Translational Pharmacology, National Research Council, 09010, Pula, Cagliari, Italy., Asproni B; Department of Chemistry and Pharmacy, University of Sassari, Via F. Muroni 23/A, 07100, Sassari, Italy., Pinna GA; Department of Chemistry and Pharmacy, University of Sassari, Via F. Muroni 23/A, 07100, Sassari, Italy.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 May 25; Vol. 152, pp. 401-416. Date of Electronic Publication: 2018 Apr 17.
DOI: 10.1016/j.ejmech.2018.04.026
Abstrakt: The cholinergic pathways in the central nervous system (CNS) of animals and humans are important for cognitive and behavioural functions. Until a few years ago, it was thought that the key molecules transducing the cholinergic message were the metabotropic muscarinic receptors, but it is now known that ionotropic neuronal nicotinic receptors (nAChRs) are also involved. Based on recent studies, we prepared a small library of novel 3-substituted-3,6-diazabicyclo [3.1.1]heptanes, whose binding activity and functionality have been assayed. Among the synthesized compounds, the 3-(anilino)pyridine series resulted in the most interesting compounds with α 4 β 2 K i values ranging from 0.0225 nM (12g) to 2.06 nM (12o).
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Databáze: MEDLINE
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