On the basis of some benzo[d]oxazol-2(3H)-one derivatives previously developed by us and gifted with excellent σ1 affinity and selectivity, we have synthesized a new series of compounds 1 and 2, changing the benzoxazolone moiety with similar groups to evaluate their effects toward the sigma affinity and selectivity. With the aim to discover some new sigma 2 ligands, we try to modulate the selectivity and the affinity of the compounds towards the two receptor subtypes changing the middle piperidinemethyl spacer (1a-j) with a less constrained butylaminomethyl chain (2 a-j). A preliminarly binding study (Discovery studio 2.5) of the p-fluoro derivatives of both series confirm the interactions between the structure of our new derivatives and the features of the σ1 3D-receptor model (Fig.1). Furthermore an initial binding test was performed for the compound 1d (p-F) which gave Ki values of 67 nM and 286 nM for σ1 and σ2 respectively. The evaluation on the complete series is still in progress.

New heterocyclic derivatives of benzylpiperidin-4-yl methyl and benzyl(methyl)aminobutyl sequences as sigma ligands.

ZAMPIERI, DANIELE;LAURINI, ERIK;PRICL, SABRINA;VIO, LUCIANO;MAMOLO, MARIA GRAZIA
2013

Abstract

On the basis of some benzo[d]oxazol-2(3H)-one derivatives previously developed by us and gifted with excellent σ1 affinity and selectivity, we have synthesized a new series of compounds 1 and 2, changing the benzoxazolone moiety with similar groups to evaluate their effects toward the sigma affinity and selectivity. With the aim to discover some new sigma 2 ligands, we try to modulate the selectivity and the affinity of the compounds towards the two receptor subtypes changing the middle piperidinemethyl spacer (1a-j) with a less constrained butylaminomethyl chain (2 a-j). A preliminarly binding study (Discovery studio 2.5) of the p-fluoro derivatives of both series confirm the interactions between the structure of our new derivatives and the features of the σ1 3D-receptor model (Fig.1). Furthermore an initial binding test was performed for the compound 1d (p-F) which gave Ki values of 67 nM and 286 nM for σ1 and σ2 respectively. The evaluation on the complete series is still in progress.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2769596
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