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
2013-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.