Discovery and first-time disclosure of CVN766, an exquisitely selective orexin 1 receptor antagonist

Bioorg Med Chem Lett. 2024 Jan 30;100:129629. doi: 10.1016/j.bmcl.2024.129629. Online ahead of print.ABSTRACTModulators of orexin receptors are being developed for neurological illnesses such as sleep disorders, addictive behaviours and other psychiatric diseases. We herein describe the discovery of CVN766, a potent orexin 1 receptor antagonist that has greater than 1000-fold selectivity for the orexin 1 receptor over the orexin 2 receptor and demonstrates low off target hits in a diversity screen. In agreement with its in vitro ADME data, CVN766 demonstrated moderate in vivo clearance in rodents and displayed good brain permeability and target occupancy. This drug candidate is currently being investigated in clinical trials for schizophrenia and related psychiatric conditions.PMID:38295907 | DOI:10.1016/j.bmcl.2024.129629

Source: Bioorganic and Medicinal Chemistry Letters - January 31, 2024 Category: Chemistry Authors: Angela Glen Roland W B ürli David Livermore William Buffham Stephanie Merison Anna E Rowland Robert Newman Charlotte Fieldhouse David J Miller Lee A Dawson Kim Matthews Mark B Carlton Nicola L Brice Source Type: research