Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists
| Autor: | Kevin Guertin, Tonika Bohnert, Tao Wang, Howard Jones, Edward Yin-Shiang Lin, Daliya Banerjee, Tina Talreja, Istvan J. Enyedy, Kurt Van Vloten, Douglas Marcotte, Jianhua Chao, Jason D. Fontenot |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Drug Inverse Agonism Clinical Biochemistry Pharmaceutical Science Inflammation Pyrazole Pharmacology Biochemistry Autoimmune Diseases Pathogenesis chemistry.chemical_compound Mice Drug Discovery Gene expression medicine Moiety Inverse agonist Animals Humans Molecular Biology Chemistry Organic Chemistry Interleukin-17 Nuclear Receptor Subfamily 1 Group F Member 3 Nuclear receptor Benzamides Molecular Medicine Pyrazoles Th17 Cells Interleukin 17 medicine.symptom Spleen |
| Zdroj: | Bioorganicmedicinal chemistry letters. 25(15) |
| ISSN: | 1464-3405 |
| Popis: | The nuclear receptor RORγ plays a central role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including TH17 cells. RORγ-dependent inflammation has been implicated in the pathogenesis of several major autoimmune diseases and thus RORγ is an attractive target for therapeutic intervention in these diseases. Starting from a lead biaryl compound 4a, replacement of the head phenyl moiety with a substituted aminopyrazole group resulted in a series with improved physical properties. Further SAR exploration led to analogues (e.g., 4j and 5m) as potent RORγ inverse agonists. |
| Databáze: | OpenAIRE |
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