Identification of N-sulfonyl-tetrahydroquinolines as RORc inverse agonists.
Basic Information
ID: ALA3616373
Journal: Bioorg Med Chem Lett
Title: Identification of N-sulfonyl-tetrahydroquinolines as RORc inverse agonists.
Authors: Fauber BP, Gobbi A, Savy P, Burton B, Deng Y, Everett C, La H, Johnson AR, Lockey P, Norman M, Wong H.
Abstract: A high-throughput screen of the Genentech/Roche compound collection using a retinoic acid receptor-related orphan receptor C (RORc, RORγ, or NR1F3) biochemical assay revealed a N-sulfonyl-tetrahydroquinoline hit. Herein, we describe the hit-to-lead optimization and structure-activity relationships of these tetrahydroquinoline RORc inverse agonists. Through iterative synthesis and analog design, we identified compounds with improved biochemical RORc inverse agonist activity and RORc cellular potencies. These improved N-sulfonyl-tetrahydroquinoline compounds also exhibited selectivity for RORc over other nuclear receptors.
CiteXplore: 26321361
DOI: 10.1016/j.bmcl.2015.08.028
Patent ID: ┄