Spiro[1,2,4-benzotriazine-3(4H),4′-(1′-substituted)piperidines] and related compounds as ligands for sigma receptors

As analogues of some conformationally restricted spiropiperidine derivatives which are endowed with high affinity for sigma(1), receptor, a set of 16 spiro[1,2,4-benzotriazine-3(4H),4'-(1'-substituted)piperidines] and congeneric compounds was prepared and tested for affinity to a, receptor subtype. All N-arylalkyl substituted derivatives exhibited high affinity for the relevant receptor, with K-i in the low nanomolar range. Affinity for sigma(2) subtype (assayed only for a few representative compounds) was from one to three order of magnitude lower. Spiro[ 1,2,4-benzotriazine-3(4H),4'-(1'-benzyl)piperidine] (2), with a ratio K(i)sigma(2)/K(j)sigma(1) = 7000 should represent the most selective sigma(1), ligand so far described. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.