Corticotropin-releasing factor (CRF) is a 41-amino acid peptide that acts as the prime regulator of the hypothalamic-pituitary-adrenal (HPA) axis. CRF is a major modulator of the body's overall response to stressors and there is evidence supporting the hypothesis that over production of CRF may underlie the pathology of stress-related disorders, such as depression and anxiety. CRF1 receptor is the most abundant subtype found in the pituitary and is involved in the regulation of adrenocorticotropic hormone (ACTH), a key mediator of the body's response to stress. Therefore a CRF1 receptor antagonist is hypothesized to be a valuable target for the treatment of stress-related disorders.To date, several CRF1 receptor antagonists have been reported and prototypical antagonists have common structural features. Here we report the generation of 5-alkylaminoquinolines as novel CRF1 receptor antagonists that have distinctive structural features compared to the currently known antagonists.

Design, synthesis and structure�activity relationships of 5-alkylaminoquinolines: Potent, orally active corticotropin-releasing factor-1 receptor antagonists

247th National Meeting (2014)

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