Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 1;25(23):5555-60.
doi: 10.1016/j.bmcl.2015.10.055. Epub 2015 Oct 19.

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

Dirk Behnke  1 , Simona Cotesta  2 , Samuel Hintermann  2 , Markus Fendt  3 , Christine E Gee  3 , Laura H Jacobson  4 , Grit Laue  5 , Arndt Meyer  2 , Trixie Wagner  2 , Sangamesh Badiger  6 , Vinod Chaudhari  6 , Murali Chebrolu  6 , Chetan Pandit  6 , Daniel Hoyer  7 , Claudia Betschart  2
Affiliations

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

Dirk Behnke et al. Bioorg Med Chem Lett. .

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.

Keywords: Antagonists; GPCRs; Insomnia; Orexin.

PubMed Disclaimer

LinkOut - more resources