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