Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel, potent and selective GABAA α5 inverse agonist series

Abstract Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5- a ][1,2,4]-triazolo[1,5- d ][1,4]benzodiazepine was deemed the most promising GABA A α5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation towards a central nervous system (CNS) acting medicine.