Behnke, Dirk, Cotesta, Simona, Hintermann, Samuel, Fendt, Markus, Gee, Christine, Jacobson, Laura, Laue, Grit, Meyer, Arndt, Wagner, Beatrix, Badiger, Sangamesh, Chaudhari, Vinod, Chebrolu, Murali, Pandit, Chetan, Hoyer, Daniel and Betschart, Claudia (2015) Discovery of 1H-pyrazolo[3,4-b]pyridines as potent dual orexin receptor antagonists (DORAs). Bioorganic and Medicinal Chemistry Letters, 25 (23). pp. 5555-5560. ISSN 0960-894X

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.

Item Type:	Article
Keywords:	Orexin, GPCRs, insomnia, antagonists
Date Deposited:	14 Nov 2015 00:45
Last Modified:	14 Nov 2015 00:45
URI:	https://oak.novartis.com/id/eprint/26372