Here, we describe the identification and synthesis of novel indole sulfonamide 
derivatives that activate the three peroxisome proliferator activated receptor 
(PPAR) isoforms. Starting with a PPARα activator, compound 4, identified during 
a high throughput screening (HTS) of our proprietary screening library, a 
systematic optimization led to the discovery of lanifibranor (IVA337) 5, a 
moderately potent and well balanced pan PPAR agonist with an excellent safety 
profile. In vitro and in vivo, compound 5 demonstrated strong activity in models 
that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology 
suggesting therapeutic potential for NASH patients.