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 sigma1 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 sigma1 receptor subtype. All N-arylalkyl substituted derivatives exhibited high affinity for the relevant receptor, with Ki in the low nanomolar range. Affinity for sigma2 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 Ki sigma2/Ki sigma1 = 7000 should represent the most selective sigma1 ligand so far described.