Imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepines as potent and highly selective GABAA alpha5 inverse agonists with potential for the treatmen...

Basic Information

ID: ALA1154267

Journal: Bioorg Med Chem Lett

Title: Imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepines as potent and highly selective GABAA alpha5 inverse agonists with potential for the treatment of cognitive dysfunction.

Authors: Buettelmann B, Ballard TM, Gasser R, Fischer H, Hernandez MC, Knoflach F, Knust H, Stadler H, Thomas AW, Trube G.

Abstract: In a search for GABAA alpha5 ligands that combine high subtype binding selectivity with a marked inverse agonism imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepines were identified as a promising class. A short tandem reaction allowed rapid access to this chemical series, thereby facilitating rapid SAR generation which guided the optimization process. Two compounds (10e and 11f) were found to be active in an in vivo paradigm for cognitive improvement.

CiteXplore: 19740657

DOI: 10.1016/j.bmcl.2009.08.027

Patent ID: