We report the design, synthesis and binding evaluation against σ1 and σ2 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on σ receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward σ1 and σ2 receptors. Very high σ1 affinity (Ki = 3.7 nM) and Kiσ2/Kiσ1 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom.

Improving selectivity preserving affinity: New piperidine-4-carboxamide derivatives as effective sigma-1-ligands

ZAMPIERI, DANIELE;LAURINI, ERIK;VIO, LUCIANO;FERMEGLIA, MAURIZIO;PRICL, SABRINA;MAMOLO, MARIA GRAZIA
2015-01-01

Abstract

We report the design, synthesis and binding evaluation against σ1 and σ2 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on σ receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward σ1 and σ2 receptors. Very high σ1 affinity (Ki = 3.7 nM) and Kiσ2/Kiσ1 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2829592
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