Novel substituted tetrahydrotriazaacenaphthylene derivatives as potent CRF1 receptor antagonists.
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.
Gentile
Gabriella
G
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithkline, Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy. gg87301@gsk.com
Di Fabio
Romano
R
Pavone
Francesca
F
Sabbatini
Fabio Maria
FM
St-Denis
Yves
Y
Zampori
Maria Grazia
MG
Vitulli
Giovanni
G
Worby
Angela
A
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
D009281:Naphthalenes; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D000099052:CRF Receptor, Type 1