Synthesis and receptor binding studies of some new arylcarboxamide derivatives as sigma-1 ligands.
We describe here the synthesis and the binding interaction with σ1 and σ2 receptors of a series of new arylcarboxamide derivatives variously substituted on the aromatic portions. Maintaining a partial scaffold of a series of compounds previously synthesized by us, we evaluate the effect of the substitution on σ binding. The synthesized compounds have been tested to estimate their affinity and selectivity toward σ1 and σ2 receptors. Two out of 16 derivatives showed an interesting σ1 affinity (21.2 and 13.6 nM-compounds 2m and 2p) and a good selectivity (Ki(σ2)/Ki(σ1) >140 and >40, respectively).
Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy. Electronic address: dzampieri@units.it.
Daniele
D
Zampieri
Molecular Simulation Engineering (MOSE) Laboratory, DI3, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy. Electronic address: erik.laurini@di3.units.it.
Erik
E
Laurini
Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Luciano
L
Vio
Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Samuel
S
Golob
Molecular Simulation Engineering (MOSE) Laboratory, DI3, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Maurizio
M
Fermeglia
Molecular Simulation Engineering (MOSE) Laboratory, DI3, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy. Electronic address: sabrina.pricl@di3.units.it.
Sabrina
S
Pricl
Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy.
Maria Grazia
MG
Mamolo
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008024:Ligands; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
D000577:Amides; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor
Arylcarboxamide derivatives; Radioligand binding assays; σ-Receptors