Synthesis and pharmacological evaluation of 6-piperidino- and 6-piperazinoalkyl-2(3H)-benzothiazolones as mixed sigma/5-HT(1A) ligands

Bioorg Med Chem Lett. 2002 Apr 22;12(8):1149-52. doi: 10.1016/s0960-894x(02)00123-3.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Evaluation, Preclinical
  • Ligands
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Receptors, sigma / metabolism*
  • Thiazoles / chemical synthesis*
  • Thiazoles / metabolism
  • Thiazoles / pharmacology*

Substances

  • Ligands
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Receptors, sigma
  • Thiazoles