Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

Y St-Denis; R Di Fabio; G Bernasconi; E Castiglioni; S Contini; D Donati; E Fazzolari; G Gentile; D Ghirlanda; C Marchionni; F Messina; F Micheli; F Pavone; A Pasquarello; F M Sabbatini; M G Zampori; R Arban; G Vitulli

doi:10.1016/j.bmcl.2005.05.040

Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3713-6. doi: 10.1016/j.bmcl.2005.05.040.

Authors

Y St-Denis¹, R Di Fabio, G Bernasconi, E Castiglioni, S Contini, D Donati, E Fazzolari, G Gentile, D Ghirlanda, C Marchionni, F Messina, F Micheli, F Pavone, A Pasquarello, F M Sabbatini, M G Zampori, R Arban, G Vitulli

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline Medicines Research Center, Via A. Fleming 4, 37135 Verona, Italy. yves.a.stdenis@gsk.com

PMID: 15946843
DOI: 10.1016/j.bmcl.2005.05.040

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.

MeSH terms

Acenaphthenes / chemical synthesis
Acenaphthenes / pharmacology*
Acenaphthenes / therapeutic use*
Animals
Anxiety / drug therapy*
Depression / drug therapy*
Disease Models, Animal
Drug Evaluation, Preclinical
Molecular Structure
Rats
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Acenaphthenes
Receptors, Corticotropin-Releasing Hormone
CRF receptor type 1