Discovery of 1H-pyrazolo[3, 4-b]pyridines as potent dual orexin receptor antagonists (DORAs). Issue 23 (1st December 2015) - Behnke, Dirk
Graphical abstract: 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.