title: Preparation of fluorescent nonpeptidic neuropeptide Y receptor ligands: analogues of the quinazoline-type anti-obesity Y5 antagonist CGP 71683A.
abstract: As part of a programme to develop fluorescence-based methods for the study of the interactions between G-protein coupled receptors (GPCRs) and their ligands the preparation of low molecular weight fluorescence-labelled neuropeptide Y (NPY) Y(5) antagonists is reported. The naphthylsulfonyl group in the potent quinazoline-type NPY Y(5) receptor antagonist CGP 71683A was replaced with a dansyl, nitrobenzoxadiazole (NBD) or acridine-9-carbonyl group. In radioligand binding studies on human Y(5) receptor expressing HEC-1B cells the substances labelled with acridine (K(i) 311 nM) and NBD (K(i) > 1000 nM) proved to be moderately active or inactive, respectively. By contrast, a K(i) value of 49 nM was found for the dansyl analogue compared to 2 nM for CGP 71683A. No binding to Y(1) receptors (SK-N-MC cells, displacement of [(3)H]propionyl-NPY) was detected for the new compounds at concentrations </= 1 microM.
authors.affiliation: College of Pharmaceutical Sciences, Peking University, 100083, Beijing, PR China.
authors.forename: Liantao
authors.initials: L
authors.lastname: Li
authors.forename: Matthias
authors.initials: M
authors.lastname: Mayer
authors.forename: Erich
authors.initials: E
authors.lastname: Schneider
authors.forename: Elvira
authors.initials: E
authors.lastname: Schreiber
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
mesh_terms: D002460:Cell Line; D006801:Humans; D008024:Ligands; D009281:Naphthalenes / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008024:Ligands; D009281:Naphthalenes; D011743:Pyrimidines; D011799:Quinazolines; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; C116786:CGP 71683 A