Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel, potent and selective GABA(A) alpha 5 inverse agonist series

作者：Achermann Guido; Ballard Theresa M; Blasco Francesca; Broutin Pierre Emmanuel; Buettelmann Bernd; Fischer Holger; Graf Martin; Hernandez Maria Clemencia; Hilty Peter; Knoflach Frederic; Koblet Andreas; Knust Henner; Kurt Anke; Martin James R; Masciadri Raffaello; Porter Richard H P; Stadler Heinz; Thomas Andrew W^*; Trube Gerhard; Wichmann Juergen

来源：Bioorganic & Medicinal Chemistry Letters, 2009, 19(19): 5746-5752.

DOI：10.1016/j.bmcl.2009.07.153

• GABA(A) receptor
• Benzodiazepines
• Cognition
• Imidazole
• Triazole
• Medicinal chemistry

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) alpha 5 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.

• 出版日期2009-10-1