A reversed sulfonamide series of selective RORc inverse agonists
Monique B van Niel1, Benjamin P Fauber2, Matthew Cartwright1
1Argenta, Early Discovery, Charles River, 7-9 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, United Kingdom.
Abstract:
The identification of a new series of RORc inverse agonists is described. Comprehensive structure-activity relationship studies of this reversed sulfonamide series identified potent RORc inverse agonists in biochemical and cellular assays which were also selective against a panel of nuclear receptors. Our work has contributed a compound that may serve as a useful in vitro tool to delineate the complex biological pathways involved in signalling through RORc. An X-ray co-crystal structure of an analogue with RORc has also provided useful insights into the binding interactions of the new series.
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