Journal article
Discovery of 1H-pyrazolo[3,4-b]pyridines as potent dual orexin receptor antagonists (DORAs)
D Behnke, S Cotesta, S Hintermann, M Fendt, CE Gee, LH Jacobson, G Laue, A Meyer, T Wagner, S Badiger, V Chaudhari, M Chebrolu, C Pandit, D Hoyer, C Betschart
Bioorganic and Medicinal Chemistry Letters | Published : 2015
Abstract
Compound rac-1 was identified by high throughput screening. Here we report SAR studies and MedChem optimization towards the highly potent dual orexin receptor antagonists (S)-2 and (S)-3. Furthermore, strategies to overcome the suboptimal physicochemical properties are highlighted and the pharmacokinetic profiles of representative compounds is presented.