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Corticotropin-releasing factor 1 receptor antagonists: a patent review
1Neurocrine Biosciences, Medicinal Chemistry, 12780 El Camino Real, San Diego, CA 92130, USA. jwilliams@neurocrine.com
Introduction:
Corticotropin-releasing factor (CRF) is a 41 amino acid peptide hypothalamic factor that plays a key role in the body's response to stress. The receptors for CRF (CRF₁ and CRF₂) are members of the class B G-protein coupled receptor family and several small molecule antagonists have been evaluated clinically in stress-related disorders.
Areas Covered:
The present review covers the disclosures of non-peptide CRF₁ antagonists in the patent literature since 2006.
Expert Opinion:
Antagonists of the CRF₁ receptor have failed to demonstrate clinical utility. All of the compounds evaluated are similar structures and are allosteric inhibitors of the CRF₁ receptor. Further clinical evaluation of new compounds appears unlikely unless novel structures are identified that interact with the receptor distinct to the first-generation antagonists.
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