Bioorg Med Chem Lett. 2007 Sep 15;17(18):5218-21. Epub 2007 Jun 30.

Novel substituted tetrahydrotriazaacenaphthylene derivatives as potent CRF1 receptor antagonists.

Gentile G, Di Fabio R, Pavone F, Sabbatini FM, St-Denis Y, Zampori MG, Vitulli G, Worby A.

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Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithkline, Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy. gg87301@gsk.com

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.

PMID:: 17629700; [PubMed - indexed for MEDLINE]

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