Journal
CHEMMEDCHEM
Volume 13, Issue 4, Pages 321-337Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201700758
Keywords
interleukin17; lipophilic ligand efficiency; psoriasis; ROR; topical application
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With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor ROR has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent ROR inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with invivo activity in an IL-23-induced mouse skin inflammation model.
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