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

doi:10.1016/j.bmcl.2015.10.055

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

Beteiligte Einrichtungen

Institut für Synaptische Physiologie

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.

Bibliografische Daten

Originalsprache	Englisch
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2015.10.055
Status	Veröffentlicht - 01.12.2015

PubMed	26522950