2. Academic Validation
  3. The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction

The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction

  • Bioorg Med Chem Lett. 2009 Oct 15;19(20):5940-4. doi: 10.1016/j.bmcl.2009.08.053.
Henner Knust 1,  Guido Achermann,  Theresa Ballard,  Bernd Buettelmann,  Rodolfo Gasser,  Holger Fischer,  Maria-Clemencia Hernandez,  Frédéric Knoflach,  Andreas Koblet,  Heinz Stadler,  Andrew W Thomas,  Gerhard Trube,  Pius Waldmeier
Affiliations

Affiliation

  • 1 F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. henner.knust@roche.com
PMID: 19762240 DOI: 10.1016/j.bmcl.2009.08.053
Abstract

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 GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models.

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