title: Synthesis and biological evaluation of pyridazino[4,3-b]indoles and indeno[1,2-c]pyridazines as new ligands of central and peripheral benzodiazepine receptors.
abstract: A large number of pyridazino[4,3-b]indoles and indeno[1,2-c]pyridazines were synthesised and tested to evaluate their binding affinities at both central (CBR) and peripheral (PBR) benzodiazepine receptors. Relatively good PBR binding affinities were found for ligands belonging to the 3-arylmethyloxy-pyridazinoindole series, whereas only 2-aryl-indenopyridazines 7a, 8a and 10a display a weak binding affinity for CBR. To find out the main structural determinants affecting PBR affinity, a molecular modelling study based on the comparative analysis of the three-dimensional properties of four properly selected derivatives 24a, 3b, 18a and 10d, with those of highly active and selective PBR ligands, taken as reference, was performed.
authors.affiliation: Dipartimento Farmacochimico, Università di Bari, via E Orabona 4, 70126 Bari, Italy. campagna@farmchim.uniba.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Campagna
authors.forename: Fausta
authors.initials: F
authors.lastname: Palluotto
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Mascia
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Maciocco
authors.forename: Carla
authors.initials: C
authors.lastname: Marra
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrieri
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D011724:Pyridazines / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D011724:Pyridazines; D011963:Receptors, GABA-A