Back to Search
Start Over
Discovery of 1 H -pyrazolo[3,4- b ]pyridines as potent dual orexin receptor antagonists (DORAs)
- Source :
- Bioorganic & Medicinal Chemistry Letters. 25:5555-5560
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- Pyridines
High-throughput screening
Clinical Biochemistry
Dual Orexin Receptor Antagonists
Administration, Oral
Pharmaceutical Science
Pharmacology
Crystallography, X-Ray
Doras
Biochemistry
Mice
Drug Discovery
Animals
Molecular Biology
G protein-coupled receptor
Molecular Structure
biology
Chemistry
Drug discovery
Orexin Receptor Antagonists
Organic Chemistry
biology.organism_classification
Orexin
Pyrazoles
Molecular Medicine
Administration, Intravenous
Protein Binding
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....683f840d5741ac67440ee89e98efc728
- Full Text :
- https://doi.org/10.1016/j.bmcl.2015.10.055