Corticotropin-releasing factor (CRF) can be considered a very important hormone or a
chemical mediator. It works closely with other systems to regulate the manner through which the body
may respond to stress. Thus it affects many biological processes associated with stress. Dysfunction of
this system has also been correlated with various diseases such as major depression, anxiety, drug addiction
and eating disorders. Rationally, this means that interfering with binding of CRF to its intended
receptors can be an attractive target for drug design aiming at developing new medications for many
ailments that are associated with stress such as depression, anxiety and stress-induced relapse in drug
addiction. Hundreds of accounts of small molecule antagonists have appeared in the literature and the
preclinical and clinical pharmacology have been reported for many of these agents. Several classes of
small molecule CRF receptor antagonists which belong to the non-peptide class have been developed
with many being widely used for research purposes. Currently several major pharmaceutical companies
are pursuing development of small non-peptide CRF1 receptor antagonists. In this review article we
explain the importance of development of non-peptide CRF antagonists and their clinical relevance with
emphasis on those members that showed great promise or those that were advanced to clinical trials.
Keywords: CRF antagonists, depression, anxiety, drug addiction, pyrimidines, hormone.
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