title: Synthesis of some 2-aryl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones as tools to define the essential pharmacophoric descriptors of a benzodiazepine receptor ligand.
abstract: The synthesis and benzodiazepine receptor (BZR) affinity of some 1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones, 2-22, are reported. Compounds 2-22 are devoid of the proton donor group, which according to a BZR schematic model was one of the pharmacophoric descriptors for receptor-ligand interaction. The binding data show that 2-(2-fluorophenyl)-9-chloro-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5 -one (12) and some other compounds display nanomolar BZR affinity, indicating that the hydrogen donor group is not essential for the anchoring of 6,6,5-tricyclic systems to the BZR but only affects the potency of a ligand.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Catarzi
authors.forename: L
authors.initials: L
authors.lastname: Cecchi
authors.forename: V
authors.initials: V
authors.lastname: Colotta
authors.forename: G
authors.initials: G
authors.lastname: Filacchioni
authors.forename: F
authors.initials: F
authors.lastname: Varano
authors.forename: C
authors.initials: C
authors.lastname: Martini
authors.forename: L
authors.initials: L
authors.lastname: Giousti
authors.forename: A
authors.initials: A
authors.lastname: Lucacchini
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D005445:Flunitrazepam / Q000378:metabolism; D008024:Ligands; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D008024:Ligands; D010078:Oxazines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam