title: N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor.
abstract: We report the synthesis and the affinity data at both the peripheral (PBR) and the central benzodiazepine receptors of a series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives III, designed as conformationally constrained analogues of 2-phenylindole-3-acetamides II such as FGIN-1-27. Most of the new compounds showed a high specificity and affinity for PBR, with K(i) in the nanomolar to subnanomolar range. The most potent ligands (4-7, 9, 13-27) stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classical ligands. The SARs of this new class of compounds are discussed.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
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: Francesca
authors.initials: F
authors.lastname: Simorini
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Patrizi
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Greco
authors.forename: Enrico
authors.initials: E
authors.lastname: Abignente
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Beatrice
authors.initials: B
authors.lastname: Chelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D006038:Glyoxylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006038:Glyoxylates; D007211:Indoles; D008024:Ligands; D011963:Receptors, GABA-A