Journal article

Discovery of 1H-pyrazolo[3,4-b]pyridines as potent dual orexin receptor antagonists (DORAs)

Dirk Behnke, Simona Cotesta, Samuel Hintermann, Markus Fendt, Christine E Gee, Laura H Jacobson, Grit Laue, Arndt Meyer, Trixie Wagner, Sangamesh Badiger, Vinod Chaudhari, Murali Chebrolu, Chetan Pandit, Daniel Hoyer, Claudia Betschart

Bioorganic & Medicinal Chemistry Letters | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2015


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.