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.
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.
Catarzi
D
D
Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Italy.
Cecchi
L
L
Colotta
V
V
Filacchioni
G
G
Varano
F
F
Martini
C
C
Giousti
L
L
Lucacchini
A
A
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
D008024:Ligands; D010078:Oxazines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam