title: Synthesis and evaluation of pharmacological properties of novel annelated 2,3-benzodiazepine derivatives.
abstract: New cyclofunctionalized 2,3-benzodiazepines characterized by a triazolone or triazindione ring fused on the "c" edge of the heptatomic nucleus have been prepared. These compounds were evaluated as potential anticonvulsant agents, and some of them proved to be more potent noncompetitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) receptor antagonists. In particular, 8,9-dimethoxy-6-(4-bromophenyl)-11H-[1,2,4]triazolo[4,5-c][2,3]benzodiazepin-3(2H)-one (5b) was almost 10-fold more active than GYKI-52466 and 3.5-fold more active than Talampanel. Furthermore, 5b potently reduced AMPA-evoked currents in electrophysiological experiments.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. gittoros@pharma.unime.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Valérie
authors.initials: V
authors.lastname: Orlando
authors.forename: Silvana
authors.initials: S
authors.lastname: Quartarone
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Angela
authors.initials: A
authors.lastname: De Sarro
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Guido
authors.initials: G
authors.lastname: Ferreri
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008811:Mice, Inbred DBA; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009833:Olfactory Pathways / Q000166:cytology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: C477014:8,9-dimethoxy-6-(4-bromophenyl)-11H-(1,2,4)triazolo(4,5-c)(2,3)benzodiazepin-3(2H)-one; D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D014230:Triazoles; D001569:Benzodiazepines; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid