Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Wang, Tao; Banerjee, Daliya; Bohnert, Tonika; Chao, Jianhua; Enyedy, Istvan; Fontenot, Jason; Guertin, Kevin; Jones, Howard; Lin, Edward Y.; Marcotte, Douglas; Talreja, Tina; Van Vloten, Kurt
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 15(2015)
• Page Start: 2985
• Page End: 2990
• Publication Date: 2015-08-01
• Subjects: RORγ inverse agonist -- IL-17 -- Inflammation -- Autoimmune disease -- Th17 cell; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.028
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 compound4a, 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 and5m ) as potent RORγ inverse agonists.