Literature

Abstract

A high-throughput screen against Inventiva's compound library using a Gal4/RORγ-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORγ inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein.

DOI： 10.1016/j.bmcl.2019.05.015

Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORγ inverse agonists

Bioorganic & Medicinal Chemistry Letters 2019.0

Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation

European Journal of Medicinal Chemistry 2014.0

Discovery of biaryls as RORγ inverse agonists by using structure-based design

Bioorganic & Medicinal Chemistry Letters 2016.0

Identification of the first inverse agonist of retinoid-related orphan receptor (ROR) with dual selectivity for RORβ and RORγt

Bioorganic & Medicinal Chemistry Letters 2014.0

Discovery of aryl-substituted indole and indoline derivatives as RORγt agonists

European Journal of Medicinal Chemistry 2019.0

Discovery of imidazo[1,5-a]pyridines and -pyrimidines as potent and selective RORc inverse agonists