Small molecule corticotropin-releasing factor antagonists

Corticotropin-releasing factor (CRF) is a 41-amino acid peptide neurohormone that plays a major role in the body's response to stress by modulating the endocrine, autonomic, behavioural and immune systems. The peptide interacts with two known receptors, CRF, and CRF2, which belong to class B (secretin-like) G-protein-coupled receptors. Over the past ten years, a number of small molecule antagonists have been published in the patent literature. The present review covers recent patent literature (since 2000) where low molecular weight, non-peptide CRF antagonists are disclosed. These can be divided into four main classes of molecules: monocyclic, bicyclic and tricyclic compounds as well as a miscellaneous category, which include compounds that are unlike the traditional small molecule CRF, antagonists.