2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists

Robert W Carling; Michael G N Russell; Kevin W Moore; Andrew Mitchinson; Alexander Guiblin; Alison Smith; Keith A Wafford; George Marshall; John R Atack; Leslie J Street

doi:10.1016/j.bmcl.2006.03.081

2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3550-4. doi: 10.1016/j.bmcl.2006.03.081. Epub 2006 Apr 18.

Authors

Robert W Carling¹, Michael G N Russell, Kevin W Moore, Andrew Mitchinson, Alexander Guiblin, Alison Smith, Keith A Wafford, George Marshall, John R Atack, Leslie J Street

Affiliation

¹ Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK. robert.carling@virgin.net

PMID: 16621541
DOI: 10.1016/j.bmcl.2006.03.081

Abstract

Novel synthetic routes have been devised for the preparation of previously inaccessible 2,3,7-trisubstituted pyrazolo[1,5-d][1,2,4]triazines 2. These compounds are high affinity ligands for the GABA(A) benzodiazepine binding site and some analogues show functional selectivity for agonism at alpha3-containing receptors over alpha1-containing receptors with the lead compound being 32.

MeSH terms

Binding Sites
GABA-A Receptor Agonists*
Humans
Ligands
Molecular Structure
Pyrazoles / chemistry*
Receptors, GABA-A
Recombinant Proteins / agonists
Stereoisomerism
Structure-Activity Relationship
Triazines / chemical synthesis*
Triazines / chemistry
Triazines / pharmacology*

Substances

GABA-A Receptor Agonists
GABRA3 protein, human
Ligands
Pyrazoles
Receptors, GABA-A
Recombinant Proteins
Triazines