title: Novel substituted tetrahydrotriazaacenaphthylene derivatives as potent CRF1 receptor antagonists.
abstract: Corticotropin-releasing factor (CRF), a 41 amino acid peptide neurohormone synthesised by specific hypothalamic nuclei in the brain, is implicated in stress-related function. Antagonism of CRF(1) receptors is an attractive therapeutic approach for the treatment of depression and anxiety. Unsaturated tetrahydrotriazaacenaphthylenes of general structure 3 have been identified as potent and selective CRF(1) receptor antagonists with a suitable oral pharmacokinetic profile.
authors.affiliation: Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithkline, Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy. gg87301@gsk.com
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gentile
authors.forename: Romano
authors.initials: R
authors.lastname: Di Fabio
authors.forename: Francesca
authors.initials: F
authors.lastname: Pavone
authors.forename: Fabio Maria
authors.initials: FM
authors.lastname: Sabbatini
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Denis
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Zampori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitulli
authors.forename: Angela
authors.initials: A
authors.lastname: Worby
mesh_terms: D000284:Administration, Oral; D006801:Humans; D009281:Naphthalenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D000099052:CRF Receptor, Type 1
chemical_list: D009281:Naphthalenes; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D000099052:CRF Receptor, Type 1