title: Synthesis and pharmacological evaluation of 6-piperidino- and 6-piperazinoalkyl-2(3H)-benzothiazolones as mixed sigma/5-HT(1A) ligands.
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).
authors.affiliation: Institut de Chimie Pharmaceutique Albert Lespagnol, Université de Lille 2, 3, rue du Professeur Laguesse, F-59006, Lille, France. amouithys@ulg.ac.be
authors.forename: Ange
authors.initials: A
authors.lastname: Mouithys-Mickalad
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Poupaert
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
mesh_terms: D004353:Drug Evaluation, Preclinical; D008024:Ligands; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017480:Receptors, sigma / Q000378:metabolism*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017480:Receptors, sigma; D013844:Thiazoles