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Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABA A α5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models.
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