Discovery of biaryls as RORγ inverse agonists by using structure-based design. Issue 10 (15th May 2016)

• Record Type: Journal Article
• Authors: Enyedy, Istvan J.; Powell, Noel A.; Caravella, Justin; van Vloten, Kurt; Chao, Jianhua; Banerjee, Daliya; Marcotte, Douglas; Silvian, Laura; McKenzie, Andres; Hong, Victor Sukbong; Fontenot, Jason D.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 10(2016)
• Page Start: 2459
• Page End: 2463
• Publication Date: 2016-05-15
• Subjects: Retinoid-related orphan receptor gamma -- RORγ -- Tetrahydroquinolines -- Sulfonamides -- Biaryls; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.109
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: RORγ plays a critical role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including T cells, γδ T cells, and innate lymphoid cells. RORγ-mediated inflammation has been linked to susceptibility to Crohn's disease, arthritis, and psoriasis. Thus inverse agonists of RORγ have the potential of modulating inflammation. Our goal was to optimize two RORγ inverse agonists:T0901317 from literature and1 that we obtained from internal screening. We used information from internal X-ray structures to design two libraries that led to a new biaryl series.