title: Structure-activity relationship studies of novel pyrazolo[1,5-c][1,3]benzoxazines: synthesis and benzodiazepine receptor affinity.
abstract: Some 2-arylpyrazolo[1,5-c][1,3]benzoxazin-5-ones 1 and 5- oxopyrazolo[1,5-c][1,3]benzoxazin-2-carboxylates 2 were prepared and biologically evaluated for their binding at benzodiazepine receptor (BZR) in rat cortical membranes. Structure-activity relationship studies suggest that, although proton donor d and proton acceptor a1 are both optional pharmacophoric descriptors, at least one of them must be present for good BZR affinity. When the proton donor d is not present, the heteroatom acceptor a1 is necessary either in the tricyclic core or in the appended substituent at the C-2 to obtain sub-micromolar BZR affinity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Varano
authors.forename: D
authors.initials: D
authors.lastname: Catarzi
authors.forename: V
authors.initials: V
authors.lastname: Colotta
authors.forename: L
authors.initials: L
authors.lastname: Cecchi
authors.forename: G
authors.initials: G
authors.lastname: Filacchioni
authors.forename: A
authors.initials: A
authors.lastname: Galli
authors.forename: C
authors.initials: C
authors.lastname: Costagli
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010078:Oxazines / Q000138:chemical synthesis* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010078:Oxazines; D011720:Pyrazoles; D011963:Receptors, GABA-A