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

• Record Type: Journal Article
• Authors: Behnke, Dirk; Cotesta, Simona; Hintermann, Samuel; Fendt, Markus; Gee, Christine E.; Jacobson, Laura H.; Laue, Grit; Meyer, Arndt; Wagner, Trixie; Badiger, Sangamesh; Chaudhari, Vinod; Chebrolu, Murali; Pandit, Chetan; Hoyer, Daniel; Betschart, Claudia
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 23(2015)
• Page Start: 5555
• Page End: 5560
• Publication Date: 2015-12-01
• Subjects: Orexin -- GPCRs -- Insomnia -- Antagonists; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.10.055
• Languages: English
• ISSNs: 0960-894X

Abstract

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.