Sulfoximines as potent RORγ inverse agonists

Bioorg Med Chem Lett. 2018 May 1;28(8):1269-1273. doi: 10.1016/j.bmcl.2018.03.041. Epub 2018 Mar 17.


Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.

Keywords: Imiquimod; Psoriasis; RORγ; Sulfoximine; Topical application.

MeSH terms

  • Animals
  • Drug Inverse Agonism
  • Female
  • Humans
  • Imines / chemical synthesis
  • Imines / chemistry
  • Imines / pharmacology*
  • Ligands
  • Mice, Inbred BALB C
  • Molecular Structure
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Sulfoxides / chemical synthesis
  • Sulfoxides / chemistry
  • Sulfoxides / pharmacology*


  • Imines
  • Ligands
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Sulfonamides
  • Sulfoxides