2. Academic Validation
  3. Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate

Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate

  • J Med Chem. 2018 Mar 22;61(6):2246-2265. doi: 10.1021/acs.jmedchem.7b01285.
Benaïssa Boubia 1,  Olivia Poupardin 1,  Martine Barth 1,  Jean Binet,  Philippe Peralba,  Laurent Mounier 1,  Elise Jacquier 1,  Emilie Gauthier 1,  Valérie Lepais 1,  Maryline Chatar 1,  Stéphanie Ferry 2,  Anne Thourigny,  Fabrice Guillier 1,  Jonathan Llacer 1,  Jérome Amaudrut 1,  Pierre Dodey,  Olivier Lacombe 1,  Philippe Masson 1,  Christian Montalbetti 1,  Guillaume Wettstein 1,  Jean-Michel Luccarini 1,  Christiane Legendre,  Jean-Louis Junien 1,  Pierre Broqua 1
Affiliations

Affiliations

  • 1 Inventiva , 50 rue de Dijon , 21121 Daix , France.
  • 2 Novalix , Boulevard Sebastien Brant Bioparc , 67405 Illkirch , France.
PMID: 29446942 DOI: 10.1021/acs.jmedchem.7b01285
Abstract

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.

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