2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones: functionally selective benzodiazepine binding site ligands on the GABAA receptor

Andrew Mitchinson; John R Atack; Peter Blurton; Robert W Carling; José L Castro; Karen S Curley; Michael G N Russell; George Marshall; Ruth M McKernan; Kevin W Moore; Robert Narquizian; Alison Smith; Leslie J Street; Sally-Anne Thompson; Keith Wafford

doi:10.1016/j.bmcl.2004.04.085

2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones: functionally selective benzodiazepine binding site ligands on the GABAA receptor

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3441-4. doi: 10.1016/j.bmcl.2004.04.085.

Authors

Andrew Mitchinson¹, John R Atack, Peter Blurton, Robert W Carling, José L Castro, Karen S Curley, Michael G N Russell, George Marshall, Ruth M McKernan, Kevin W Moore, Robert Narquizian, Alison Smith, Leslie J Street, Sally-Anne Thompson, Keith Wafford

Affiliation

¹ Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow CM20 2QR, UK. andrew_mitchinson@merck.com

PMID: 15177449
DOI: 10.1016/j.bmcl.2004.04.085

Abstract

2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands with functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimise this functional selectivity are described.

MeSH terms

Animals
Benzodiazepines / chemistry
Benzodiazepines / metabolism
Binding Sites
Humans
Kinetics
Ligands
Molecular Structure
Patch-Clamp Techniques
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology
Pyridines / chemistry
Pyridines / metabolism
Radioligand Assay
Receptors, GABA-A / metabolism*
Structure-Activity Relationship

Substances

Ligands
Pyrazoles
Pyridines
Receptors, GABA-A
CGS 17867A
Benzodiazepines