title: Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety.
abstract: Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline Medicines Research Center, Via A. Fleming 4, 37135 Verona, Italy. yves.a.stdenis@gsk.com
authors.forename: Y
authors.initials: Y
authors.lastname: St-Denis
authors.forename: R
authors.initials: R
authors.lastname: Di Fabio
authors.forename: G
authors.initials: G
authors.lastname: Bernasconi
authors.forename: E
authors.initials: E
authors.lastname: Castiglioni
authors.forename: S
authors.initials: S
authors.lastname: Contini
authors.forename: D
authors.initials: D
authors.lastname: Donati
authors.forename: E
authors.initials: E
authors.lastname: Fazzolari
authors.forename: G
authors.initials: G
authors.lastname: Gentile
authors.forename: D
authors.initials: D
authors.lastname: Ghirlanda
authors.forename: C
authors.initials: C
authors.lastname: Marchionni
authors.forename: F
authors.initials: F
authors.lastname: Messina
authors.forename: F
authors.initials: F
authors.lastname: Micheli
authors.forename: F
authors.initials: F
authors.lastname: Pavone
authors.forename: A
authors.initials: A
authors.lastname: Pasquarello
authors.forename: F M
authors.initials: FM
authors.lastname: Sabbatini
authors.forename: M G
authors.initials: MG
authors.lastname: Zampori
authors.forename: R
authors.initials: R
authors.lastname: Arban
authors.forename: G
authors.initials: G
authors.lastname: Vitulli
mesh_terms: D000073:Acenaphthenes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
chemical_list: D000073:Acenaphthenes; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1