title: Geometrically constrained analogues of N-benzylindolylglyoxylylamides: [1, 2, 4]triazino[4, 3-a]benzimidazol-4(10H)-one derivatives as potential new ligands at the benzodiazepine receptor.
abstract: A series of 3-benzylamino-and 3-arylalkylaminocarbonyl [1, 2, 4]triazino [4, 3-a]benzimidazoles 1-12 were synthesized and biologically assayed as geometrically constrained analogues of N-benzylindolylglyoxylylamides II, which are high affinity ligands at the benzodiazepine receptor (BzR). The intermediate 3-ethoxycarbonyl [1, 2, 4]triazino [4, 3-a]benzimidazol-4(10H)-one 14 and its N(10)-methyl analogue 15 closely related to 3-alkoxycarbonyl-beta-carbolines I were also investigated. The title compounds exhibited a lower affinity compared with the corresponding indolylglyoxylylamide derivatives II. Attempts were made to rationalize these results taking into account the possible tautomeric equilibria involving these ligands.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Pisa, Italy. primofiore@farm.unipi.it
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Primofiore
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marini
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Greco
authors.forename: Letizia
authors.initials: L
authors.lastname: Trincavelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C480963:(1, 2, 4)triazino(4, 3-a)benzimidazol-4(10H)-one; D001562:Benzimidazoles; D007211:Indoles; D008024:Ligands; D011963:Receptors, GABA-A; D014227:Triazines; C103089:N-(indol-3-ylglyoxylyl)benzylamine