According to the World Health Organization, chronic inflammatory diseases should be regarded as one of the greatest threats to human health. Glucocorticoids have widespread use in the clinic and constitute the primary treatment option for e.g. asthma, allergy, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Unfortunately, prolonged glucocorticoid treatment at higher doses is severely hampered by side effects and a gradual emergence of resistance. Despite these problems, the glucocorticoid receptor will remain a crucial drug target in inflammation because of its efficacy, combined with the low cost of its agonists.
This project aims to synthesize metabolically stable hybrids targeting glucocorticoid receptor-based heterodimers through efficient procedures. Additionally, these novel molecules will be characterized in terms of anti-inflammatory activity, side effect marker profiles, and eADME-Tox properties, which altogether will establish their value as a novel therapeutic agents to proceed to chronic inflammation models.