Loading…
Discovery of HTL6641, a dual orexin receptor antagonist with differentiated pharmacodynamic properties
A novel series of potent, selective, and orally efficacious dual antagonists of the orexin receptors has been investigated, resulting in the identification of lead compound 27 (HTL6641). Comprehensive data for 27 are presented, including in vivo PK parameters, confirmation of receptor occupancy thro...
Saved in:
Published in: | MedChemComm 2015-05, Vol.6 (5), p.947-955 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | A novel series of potent, selective, and orally efficacious dual antagonists of the orexin receptors has been investigated, resulting in the identification of lead compound
27
(HTL6641). Comprehensive data for 27 are presented, including
in vivo
PK parameters, confirmation of receptor occupancy through
ex vivo
binding and efficacy in a rat sleep model. A key feature of the series is a short dissociation half-life, measured by surface plasmon resonance (SPR) using stabilized receptors, and confirmed by radioligand-binding experiments. Based on a consideration of the requirements for a potential treatment for insomnia, compound
27
was identified as having the best balance of properties from the chemical series. |
---|---|
ISSN: | 2040-2503 2040-2511 |
DOI: | 10.1039/C5MD00027K |