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1. Field of the Invention
The present invention relates to novel corticotropin releasing factor (CRF) antagonists.
2. Description of Related Art
The corticotropin releasing factor (CRF) is a 41 amino acid peptide first isolated and characterized by Vale et al., Science 213:1394 (1981), and further characterized and isolated by Vale et al., Science 213:1394-1398 (1981). The characterization of this peptide as the primary physiological regulator of proopiomelanocortin (POMC) derived peptide secretion provided the basis for the entire field of study on the role of CRF and its analogs in human physiology. In a broader sense, the invention of CRF antagonists has also been proposed for the treatment of anxiety, depression and related illnesses in human patients.
Vale et al. demonstrated the localization of CRF in the hypothalamus of rats and stated that CRF may play a role in the regulation of pituitary hormone release. Further studies by Imperiale et al. (Science 217:218 (1982)) confirmed the hypothalamic localization of CRF and provided a radioimmunoassay for the identification of human CRF. These studies also suggested that CRF is involved in the control of smooth muscle contractility and noted a correlation between a physiological rise in plasma CRF and fear and panic in humans.
Continued research resulted in the identification of nucleic acids encoding the CRF peptide in the hypothalamus and brain stem of several species, including man. The localization of CRF mRNA in the central nervous system (CNS) and peripheral tissues further substantiated the role of CRF as the hypothalamic release of CRF triggers pituitary hormone secretion and ultimately results in the production and release of adrenocorticotropic hormone (ACTH) which then produces the glucocorticoids.
There is a need for compounds which function as CRF antagonists, and which have the ability to inhibit CRF induced ACTH secretion. Such compounds can be useful in the diagnosis and treatment of diseases which are associated with dysregulation of the CRF and/or ACTH/cortisol secretion pathways, such as Cushing’s Syndrome, depression, anxiety, anorexia nervosa, bulimia, Alzheimer’s disease, impaired glucose tolerance, https://eqcompu.com/2022/06/07/movie-outline-crack-with-registration-code/
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