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Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis
Author(s) -
Ouvry Gilles,
AtruxTallau Nicolas,
Bihl Franck,
Bondu Aline,
BouixPeter Claire,
Carlavan Isabelle,
Christin Olivier,
Cuadrado MarieJosée,
DefoinPlatel Claire,
Deret Sophie,
Duvert Denis,
Feret Christophe,
Forissier Mathieu,
Fournier JeanFrançois,
Froude David,
HaciniRachinel Fériel,
Harris Craig Steven,
Hervouet Catherine,
Huguet Hélène,
Lafitte Guillaume,
Luzy AnnePascale,
Musicki Branislav,
Orfila Danielle,
Ozello Benjamin,
Pascau Coralie,
Pascau Jonathan,
Parnet Véronique,
Peluchon Guillaume,
Pierre Romain,
Piwnica David,
Raffin Catherine,
Rossio Patricia,
Spiesse Delphine,
Taquet Nathalie,
Thoreau Etienne,
Vatinel Rodolphe,
Vial Emmanuel,
Hennequin Laurent François
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700758
Subject(s) - inverse agonist , orphan receptor , rar related orphan receptor gamma , agonist , psoriasis , retinoic acid , pharmacology , in vivo , medicine , chemistry , receptor , immunology , biology , biochemistry , foxp3 , immune system , transcription factor , gene , microbiology and biotechnology
With possible implications in multiple autoimmune diseases, the retinoic acid receptor‐related orphan receptor RORγ has become a sought‐after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N ‐(2,4‐dimethylphenyl)‐ N ‐isobutyl‐2‐oxo‐1‐[(tetrahydro‐2 H ‐pyran‐4‐yl)methyl]‐2,3‐dihydro‐1 H ‐benzo[ d ]imidazole‐5‐sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL‐23‐induced mouse skin inflammation model.