Substituted benzyloxytricyclic compounds as retinoic acid-related orphan receptor gamma t (RORγt) agonists

Bioorg Med Chem Lett. 2020 Jun 15;30(12):127204. doi: 10.1016/j.bmcl.2020.127204. Epub 2020 Apr 20.


Substituted benzyloxy aryl compound 2 was identified as an RORγt agonist. Structure based drug design efforts resulted in a potent and selective tricyclic compound 19 which, when administered orally in an MC38 mouse tumor model, demonstrated a desired pharmacokinetic profile as well as a dose-dependent pharmacodynamic response. However, no perceptible efficacy was observed in this tumor model at the doses investigated.

Keywords: ROR gamma; RORgt; RORγt; Retinoic acid related orphan receptor; TH17 cells and IL-17.

MeSH terms

  • Animals
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Receptors, Retinoic Acid / agonists*
  • Structure-Activity Relationship


  • Benzyl Compounds
  • Heterocyclic Compounds
  • Receptors, Retinoic Acid
  • retinoic acid receptor gamma