F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland.
Bioorg Med Chem Lett. 2009 Oct 15;19(20):5958-61. doi: 10.1016/j.bmcl.2009.08.027. Epub 2009 Aug 11.
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.
在寻找 GABA A 受体 α5 配体的过程中，具有高度亚型结合选择性和显著反向激动作用的咪唑并[1,5-a][1,2,4]-三唑并[1,5-d][1,4]苯并二氮杂䓬类化合物被认为是一个很有前途的类别。通过一个短的串联反应可以快速获得这个化学系列，从而促进了快速的 SAR 生成，指导了优化过程。发现两种化合物（10e 和 11f）在认知改善的体内模型中具有活性。
