title: Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine derivatives. 3. New 6-(3-thienyl) series as alpha 1 selective ligands.
abstract: New 3-aryl-6-(3-thienyl)pyrazolo[1,5-a]pyrimidin-7-ones (2a-j) are synthesized and evaluated in vitro on Bz/GABA(A) receptors and on recombinant benzodiazepine receptors (alpha x beta 2/3 gamma 2; x = 1-3, 5) expressed in HEK293 cells. SAR studies on the new compounds are conducted and molecular modeling is accomplished to better investigate requirements leading to subtype selectivity. Some of the synthesized compounds are tested in vivo to explore their pharmacological effect as a consequence of their high alpha 1 beta 2 gamma 2 subtype selectivity observed in vitro.
authors.affiliation: Department of Pharmaceutical Sciences, University of Firenze, Via G. Capponi 9, 50121 Firenze, Italy. silvia.selleri@unifi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Selleri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bruni
authors.forename: Camilla
authors.initials: C
authors.lastname: Costagli
authors.forename: Annarella
authors.initials: A
authors.lastname: Costanzo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guerrini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ciciani
authors.forename: Paola
authors.initials: P
authors.lastname: Gratteri
authors.forename: Claudia
authors.initials: C
authors.lastname: Bonaccini
authors.forename: Petra
authors.initials: P
authors.lastname: Malmberg Aiello
authors.forename: François
authors.initials: F
authors.lastname: Besnard
authors.forename: Stephane
authors.initials: S
authors.lastname: Renard
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D008024:Ligands; D009125:Muscle Relaxants, Central; D011743:Pyrimidines; D011963:Receptors, GABA-A