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ID: ALA3596090

Journal: Bioorg Med Chem Lett

Title: Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists.

Authors: Wang T, Banerjee D, Bohnert T, Chao J, Enyedy I, Fontenot J, Guertin K, Jones H, Lin EY, Marcotte D, Talreja T, Van Vloten K.

Abstract: 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.

CiteXplore: 26048789

DOI: 10.1016/j.bmcl.2015.05.028