Synthesis and pharmacological evaluation of 6-piperidino- and 6-piperazinoalkyl-2(3H)-benzothiazolones as mixed sigma/5-HT1A ligands

In an effort to produce new pharmacological probes with mixed sigma/5-HT1A affinity, we have synthesized a series of 12 original 6-piperidino- or piperazino-alkyl-2(3H)-benzothiazolones and their receptor binding profile (sigma, 5-HT1A, 5-HT2A, 5-HT3, D-2, H-1, and M-1) was determined. The best mixed sigma/5-HT1A affinity profile was found within the piperidine series with 4-benzyl substitution associated to linker methylene chain n = 2 (K-i 5 and 4 nM, respectively). Moreover, a highly selective sigma2 ligand was obtained with a 3,4-dichlorobenzyl substitution associated to n = 4 (K-i 2 nM, selectivity ratio sigma1/sigma2 = 70). (C) 2002 Elsevier Science Ltd. All rights reserved