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J Med Chem. 2000 Aug 10;43(16):2975-81.

3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator.

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Immunological Diseases Research, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064-6217, USA.


A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a novel inhibitor of cytokine production. Identified initially as inhibitors of IL-2 synthesis, the BTPs have been optimized in this regard and even inhibit IL-2 production with a 10-fold enhancement over cyclosporine in an ex vivo assay. Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eotaxin production. Unlike the IL-2 inhibitors, cyclosporine and FK506, the BTPs do not directly inhibit the dephosphorylation of NFAT by calcineurin.

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