Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 8; pp. 2163 - 2167
• Main Authors: Thompson, Christopher F., Quraishi, Nazia, Ali, Amjad, Tata, James R., Hammond, Milton L., Balkovec, James M., Einstein, Monica, Ge, Lan, Harris, Georgianna, Kelly, Theresa M., Mazur, Paul, Pandit, Shilpa, Santoro, Joseph, Sitlani, Ayesha, Wang, Chuanlin, Williamson, Joanne, Miller, Douglas K., Yamin, Ting-ting D., Thompson, Chris M., O’Neill, Edward A., Zaller, Dennis, Forrest, Michael J., Carballo-Jane, Ester, Luell, Silvi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.04.2005; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; Dissociation; Glucocorticoid; Glucocorticoids - administration & dosage; Glucocorticoids - chemistry; Glucocorticoids - pharmacology; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Hormones. Endocrine system; Humans; Inflammation; Lipopolysaccharides - pharmacology; Medical sciences; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Rats; Transactivation; Transrepression; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis; Inflammation; Dissociation; Transrepression; Glucocorticoid; Transactivation; Steroid; Corticosteroid; Ligand; Rodentia; Antiinflammatory agent; Alcohol; In vitro; Biological activity; Benzothiophene derivatives; In vivo; Vertebrata; Mammalia; Mouse; Animal; Glucocorticoid receptor; Fluorine Organic compounds; Heterocyclic compound; Prednisolone; Hormonal receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.02.009

Compound 15 displayed the profile of a dissociated glucocorticoid in vitro and reduced inflammation in a mouse. A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse.